Mechanical and electrical manifestations of the papillary muscles of verapamil-treated adult guinea-pigs under steady state conditions and after a pause

The authors studied the effect of verapamil in 10(-7) to 10(-4) mol.l-1 concentration on the duration of action potentials (AP) and the corresponding isometric contractions (MG) from the right ventricular papillary muscles of adult guinea-pigs. In the steady state, using stimulation frequencies of 0.1, 1 and 2 Hz, verapamil caused dose- and use-dependent shortening of the AP plateau phase (D0) in 10(-5) and 10(-4) mol.l-1 concentration; lower concentrations did not affect the D0. With all the given concentrations, the MG fell in relation to the dose and the stimulation frequency. The pause regimen was defined by the induction of a steady state at 1 Hz frequency, followed by the interpolation of a pause lasting 5 s to 600 s and its effect was studied on the first and second AP after the pause and on the corresponding MG, without any pharmacological treatment and in the presence of verapamil (10(-5) mol.l-1). In the absence of the drug, slight lengthening of the D0 and weakening of the MG, proportional to the length of the pause, occurred after the pause. In the presence of verapamil, the first post-rest contraction after a 10 s pause attained five-fold the value in the steady state, while the second post-rest contraction was much weaker than the first. The possibility that verapamil acts on intracellular links in calcium metabolism, and of disproportion of its effect on the D0 and on contractility when it is administered in low concentrations, is discussed. The most likely mechanism of this effect is the presence of a negative feedback between calcium release from the sarcoplasmic reticulum and membrane electrogenesis.     

Electromechanical relationships of rabbit papillary muscle under interpolated extrasystole conditions and after a pause

The aim of the study was to describe and attempt to explain certain specific features of electromechanical coupling in the rabbit myocardium. Electromechanical correlations in the papillary muscles of the right ventricle of adult rabbit hearts were studied by a programmed stimulation technique. The duration of action potentials (AP) was measured in the plateau phase (Do, ms) and at -80 mV level (D80, ms), together with the intensity of the corresponding isometric contractions (MG, arbitrary units). After twenty AP of 1 Hz frequency, we interpolated an extrasystole with a variable interval (TE = 100-900 ms) and measured D0 and MG of the premature AP and the first AP of the subsequent cycle. When a steady state at 1 Hz frequency had been reached, we interpolated pauses (Tp) of 5 to 600 s and read D80 and MG of the first to the tenth contraction after the pause. The extrasystole D0 attained the maximum at TE = 260 ms and then fell abruptly. The MG of extrasystoles with a longer TE grew from the lowest value (0.3), attained 1 at TE = 700 ms and then remained stable. The first contraction after extrasystole displayed distinct postextrasystolic potentiation (MG = 2), while D0 was unwontedly short. Prolongation of TE was accompanied by an increase in its D0 value and by a steep drop in MG (to as little as 0.2). D80 of the first AP evoked after the pause fell proportionally to log Tp and then, from Tp = 60 s, gradually rose. The MG value of the first contraction after the pause fell proportionally to log Tp. The AP recovered much more rapidly than contractility from the effect of the pause. In the discussion, an attempt is made to explain the found correlations on the basis of differences in the behaviour of the calcium current channel system in the rabbit myocardium and a commentary on electromechanical correlations is based on the hypothesis that the free sarcoplasmic calcium level determines both membrane electrogenesis and the inotropic state.     

Action potentials of the rabbit, guinea pig, dog and albino rat working ventricular myocardium under interpolated extrasystole conditions during postnatal ontogenesis

Experiments were carried out on the working myocardium of the right heart ventricle of newborn and adult rabbits, guinea-pigs, dogs and albino rats. In the dog, the guinea-pig and the rabbit, after ten action potentials (AP) elicited with 1 Hz frequency we always interpolated an extrasystole at an interval (TE) of 100-900 ms. In albino rats we used a basic frequency of 2 Hz and a TE of 30-370 ms from the last regular AP. Using glass microelectrodes, we recorded the extrasystolic AP (EAP) and the next subsequent AP (2AP). The results were evaluated by constructing graphs of the correlations of the duration of the plateau phase (D0) to TE and of the duration of repolarization to -60 mV level (D60) to the TE. In the myocardium of newborn rabbits, guinea-pigs and dogs, with short TE both D0 and D60 of the EAP are shorter than in the steady state (SS), while for the 2AP the same parameters are influenced only a little. As the TE lengthens, the EAP gradually acquire a length corresponding more to the SS. With TE longer than half the duration of the cycle in the steady state the EAP return to normal, while the 2AP become shorter. The effect of extrasystole on the rat EAP and 2AP diminished with advancing age. In the myocardium of adult rabbits and adult guinea-pigs, and slightly in the myocardium of adult dogs and newborn rats, we observed that the duration of the EAP, with certain TE, was greater than in the steady state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Basic electrophysiological parameters and frequency sensitivity of the ventricular myocardium of human embryos

The basic electrophysiological manifestations of the ventricular myocardium of twelve 7- to 12-week human embryos were measured with a glass electrode and a programmed stimulation technique. The resting membrane potential value was 79.37 +/- 0.34 mV and the overshoot 32.7 +/- 0.57 mV; the action potential (AP) duration at 1 Hz stimulation frequency was 120.0 +/- 5.7 ms at AP plateau phase levels and 258 +/- 17 ms at the level corresponding to 95% repolarization. The duration of the AP was a function of the stimulation frequency. i.e. it altered in correlation to the stimulation programme fully developed frequency sensitivity). In stimulation with different frequencies the duration of the steady state AP was in an inverse relation to the stimulation frequency, the maximum changes being found in the terminal repolarization zone. An interpolated extrasystole mainly affected the duration of the plateau phase.     

Effect of a pause on action potentials of the working ventricular myocardium of human embryos

The effect of a period of rest (Tp) lasting from 5 to 120 s on the action potentials (AP) of the ventricular myocardium of 9- to 11-week human embryos was studied. The result was shortening of the AP proportional to the duration of the pause and it was accompanied by a shift of the AP plateau phase to more negative membrane voltages. Shortening of the AP during the pause was more pronounced in solutions with a half extracellular calcium concentration. Recovery from the effect of the pause took place significantly more slowly in solutions with the lower extracellular calcium concentration than in the presence of a normal concentration.     

The effects of KB-R7943, an inhibitor of reverse Na<Superscript>+</Superscript>/Ca<Superscript>2+</Superscript> exchange,on the force of contraction of papillary muscles in the heart of the ground squirrel <Emphasis Type="Italic">Spermophilus undulatus</Emphasis>

We investigated the effect of KB-R7943, an inhibitor of the reverse mode of Na⁺/Ca²⁺ exchanger, on the force of isometric contractions, the contractile force–frequency relationship and post-rest potentiation (a qualitative parameter of Ca²⁺ levels in sarcoplasmic reticulum) in the right ventricle papillary muscles isolated from ground squirrel hearts during summer (June, n = 4) and autumn (October, n = 4) activities. In the presence of 1.8 mM Ca2+at 36°C, 1–1.5 hours-long treatment of the summer papillary muscles with KB-R7943 produced no significant effects on the contractile indices at the majority of stimulation frequencies. In the autumn papillary muscles KB-R7943 induced a 40–50% decrease in the force of contraction (negative inotropic effect) at low stimulation frequencies (0.1–0.3 Hz) without any significant effect at higher stimulation frequencies (0.4–3.0 Hz). Furthermore, in this group, KB-R7943 suppressed the post-rest potentiation of contractility by 50 ± 21% at pause durations exceeding 120 s. These observations indicate that KB-R7943 can affect Ca²⁺ levels in sarcoplasmic reticulum and that Na⁺/Ca2⁺ exchange may contribute to the physiological remodeling of intracellular Ca²⁺ homeostasis in myocardium of hibernating animals prior their transition to a hypometabolic torpid state.     

Characteristics of force-frequency relations in the myocardium of the squirrel Citellus undulatus

The force-frequency relationship (FFR) in papillary muscles of the heart of active ground squirrel in different seasons was studied. For comparison, similar preparations from rat and rabbit were used. It was shown that the FFR of papillary muscles of active ground squirrel undergo significant seasonal changes. In summer and a part of autumn squirrels, a negative staircase (a decrease in the isometric force with increasing stimulation frequency) similar to that in adult rat was revealed. The FFR of the majority of autumn, winter and spring squirrels were polyphasic and contained both positive and negative components. Changes in the force in response to the introduction of pauses at a constant stimulation frequency were recorded. Two types of the post-rest recovery pattern were revealed in the myocardium of ground squirrels. For frequencies range with the negative direction of FFR, a typical pattern of rest-potentiation similar to that in rat papillary muscles was observed. The amplitude of the first post-rest contraction (F1) was usually higher than that of the preceding steady-state contraction. In papillary muscles of autumn animals the F1 value was greater that in summer, which suggests an enhanced release of Ca2+ from the sarcoplasmic reticulum. There was no post-rest potentiation in the range of frequencies with positive direction of FFR, and the post-rest recovery pattern in these cases was principally different from those of rat and rabbit preparations. It was proposed that seasonal differences of the FFR of active ground squirrel heart are associated with changes in the ratio of activities of the calcium-transporting system in the hibernation period.     

Extracellular calcium transients and action potential configuration changes related to post-stimulatory potentiation in rabbit atrium

Extracellular calcium transients were monitored with 2 mM tetramethylmurexide at low calcium (250 microM total, 130 microM free), and action potentials were monitored together with developed tension at normal calcium (1.3 mM) during the production and decay of post-stimulatory potentiation in rabbit left atrial strips. At normal calcium, the contractile potentiation produced by a brief burst of 4 Hz stimulation is lost in three to five post-stimulatory excitations, which correlate with a negative staircase of the late action potential. At low calcium, stimulation at 4 Hz for 3-8 s results in a net extracellular calcium depletion of 5-15 microM. At the subsequent potentiated contraction (1-45 s rest), total extracellular calcium increases by 4-8 microM. The contractile response at a second excitation is greatly suppressed and results in little or no further calcium shift; the sequence can be repeated immediately thereafter. Reducing external sodium to 60 mM (sucrose replacement) enhances post-rest contractions, suppresses the late action potential, nearly eliminates loss of contractility and net calcium efflux at post-rest excitations, and markedly reduces extracellular calcium depletion during rapid stimulation. 4-Aminopyridine (1 mM) markedly suppresses the rapid early repolarization of this preparation at post-rest excitations and the loss of contractility at post-rest stimulation from the rested state; during a post-stimulatory potentiation sequence at low calcium, replenishment of extracellular calcium takes several post-stimulatory excitations. Ryanodine (10 nM to 5 microM) abolishes the post-stimulatory contraction at rest periods of greater than 5 s. If the initial repolarization is rapid, ryanodine suppresses the late action potential, calcium efflux during quiescence is greatly accelerated, and subsequent excitations do not result in an accumulation of extracellular calcium. A positive staircase of the early action potential correlates with the magnitude of net extracellular calcium depletion. These findings demonstrate that negative contractile staircases at post-rest stimulation correspond closely to an accumulation of extracellular calcium at activation and a negative staircase of the late action potential; the correlation of these three events suggests that electrogenic sodium-calcium exchange is the common underlying mechanism.     

Contrasting effects of ischemia on the kinetics of membrane voltage and intracellular calcium transient underlie electrical alternans

Repolarization alternans has been considered a strong marker of electrical instability. The objective of this study was to investigate the hypothesis that ischemia-induced contrasting effects on the kinetics of membrane voltage and intracellular calcium transient (Ca(i)T) can explain the vulnerability of the ischemic heart to repolarization alternans. Ischemia-induced changes in action potential (AP) and Ca(i)T resulting in alternans were investigated in perfused Langendorff guinea pig hearts subjected to 10-15 min of global no-flow ischemia followed by 10-15 min of reperfusion. The heart was stained with 100 microl of rhod-2 AM and 25 microl of RH-237, and AP and Ca(i)T were simultaneously recorded with an optical mapping system of two 16 x 16 photodiode arrays. Ischemia was associated with shortening of AP duration (D) but delayed upstroke, broadening of peak, and slowed decay of Ca(i)T resulting in a significant increase of Ca(i)T-D. The changes in APD were spatially heterogeneous in contrast to a more spatially homogeneous lengthening of Ca(i)T-D. Ca(i)T alternans could be consistently induced with the introduction of a shorter cycle when the upstroke of the AP occurred before complete relaxation of the previous Ca(i)T and generated a reduced Ca(i)T. However, alternans of Ca(i)T was not necessarily associated with alternans of APD, and this was correlated with the degree of spatially heterogeneous shortening of APD. Sites with less shortening of APD developed alternans of both Ca(i)T and APD, whereas sites with greater shortening of APD could develop a similar degree of Ca(i)T alternans but slight or no APD alternans. This resulted in significant spatial dispersion of APD. The study shows that the contrasting effects of ischemia on the duration of AP and Ca(i)T and, in particular, on their spatial distribution explain the vulnerability of ischemic heart to alternans and the increased dispersion of repolarization during alternans.     

The mechanism of large, excitation-dependent influx of 45Ca in the guinea-pig ventricular myocardium

In the previous papers (Lewartowski et al. 1982; Pytkowski et al. 1983) we found that excitation-dependent uptake of 45Ca (EDU) ranges in the vascularly perfused guinea-pig ventricular myocardium from 40-359 mumol/kg of wet weight per single steady-state beat or post-rest beat. The present paper describes an attempt to find whether slow calcium channel or Na/Ca exchange provides the route of this large 45Ca influx. We found that EDU during steady-state stimulation (60/min) was completely blocked by both D-600 (1 mg/l) and Ni (2 mmol/l) whereas EDU in post-rest beats was blocked only by Ni. Low Na+ perfusion (50 mmol/l) increased transiently EDU in steady-state beats. This surplus EDU was not blocked by D-600 nor by Ni. Noradrenaline infused at the rate sufficient to increase contractile force by 50% at least doubled EDU both in the steady-state and in post-rest beats. It is proposed that Na/Ca exchange does not participate significantly to EDU under physiological conditions. The changes in this uptake evoked by the applied interventions could be expected if its route was provided by the slow Ca channel.     

Voluntary activation level and muscle fiber recruitment of human quadriceps during lengthening contractions.

Voluntary activation levels during lengthening, isometric, and shortening contractions (angular velocity 60 degrees/s) were investigated by using electrical stimulation of the femoral nerve (triplet, 300 Hz) superimposed on maximal efforts. Recruitment of fiber populations was investigated by using the phosphocreatine-to-creatine ratio (PCr/Cr) of single characterized muscle fibers obtained from needle biopsies at rest and immediately after a series of 10 lengthening, isometric, and shortening contractions (1 s on/1 s off). Maximal voluntary torque was significantly higher during lengthening (270 +/- 55 N.m) compared with shortening contractions (199 +/- 47 N.m, P < 0.05) but was not different from isometric contractions (252 +/- 47 N.m). Isometric torque was higher than torque during shortening (P < 0.05). Voluntary activation level during maximal attempted lengthening contractions (79 +/- 8%) was significantly lower compared with isometric (93 +/- 5%) and shortening contractions (92 +/- 3%, P < 0.05). Mean PCr/Cr values of all fibers from all subjects at rest were 2.5 +/- 0.6, 2.0 +/- 0.7, and 2.0 +/- 0.7, respectively, for type I, IIa, and IIax fibers. After 10 contractions, the mean PCr/Cr values for grouped fiber populations (regardless of fiber type) were all significantly different from rest (1.3 +/- 0.2, 0.7 +/- 0.3, and 0.8 +/- 0.6 for lengthening, isometric, and shortening contractions, respectively; P < 0.05). The cumulative distributions of individual fiber populations after either contraction mode were significantly different from rest (P < 0.05). Curves after lengthening contractions were less shifted compared with curves from isometric and shortening contractions (P < 0.05), with a smaller shift for the type IIax compared with type I fibers in the lengthening contractions. The results indicate a reduced voluntary drive during lengthening contractions. PCr/Cr values of single fibers indicated a hierarchical order of recruitment of all fiber populations during maximal attempted lengthening contractions.     

Autonomic cardiovascular control in conscious mice

Autonomic cardiovascular control was characterized in conscious, chronically catheterized mice by spectral analysis of arterial pressure (AP) and heart rate (HR) during autonomic blockade or baroreflex modulation of autonomic tone. Both spectra were similar to those obtained in humans, but at approximately 10x higher frequencies. The 1/f relation of the AP spectrum changed to a more shallow slope below 0.1-0.2 Hz. Coherence between AP and HR reached 0.5 or higher below 0.3-0.4 Hz and also above 2.5 Hz. Muscarinic blockade (atropine) or beta-adrenergic blockade (atenolol) did not significantly affect the AP spectrum. Atropine reduced HR variability at all frequencies, but this effect waned above 1 Hz. beta-Adrenergic blockade (atenolol) slightly enhanced the HR variability only above 1 Hz. alpha-Adrenergic blockade (prazosin) reduced AP variability between 0.05 and 3 Hz, most prominently at 0. 15-0.7 Hz. A shift of the autonomic nervous tone by a hypertensive stimulus (phenylephrine) enhanced, whereas a hypotensive stimulus (nitroprusside) depressed AP variability at 1-3 Hz; other frequency ranges of the AP spectrum were not affected except for a reduction below 0.4 Hz after nitroprusside. Variability of HR was enhanced after phenylephrine at all frequencies and reduced after nitroprusside. As with atropine, the reduction with nitroprusside waned above 1 Hz. In conclusion, in mice HR variability is dominated by parasympathetic tone at all frequencies, during both blockade and physiological modulation of autonomic tone. There is a limitation for further reduction but not for augmentation of HR variability from the resting state above 1 Hz. The impact of HR on AP variability in mice is confined to frequencies higher than 1 Hz. Limits between frequency ranges are proposed as 0.15 Hz between VLF (very low frequency range) and LF (low frequency range) and 1.5 Hz between LF and HF (high frequency range).     

Comparative studies on the positive inotropic effect of isoproterenol and bromobenzoyl-methyladamantylamine in guinea pig ventricular myocardium

The effects of bromobenzoyl-methyladamantylamine (BMA) on the transmembrane potentials, contractile force, and 42K efflux were investigated and compared to that of isoproterenol (IPR) in guinea pig ventricular myocardium. Both drugs exerted positive inotropic effect. BMA lengthened the action potential duration, depolarized the membrane, and decreased the Vmax. IPR increased the height of the plateau, accelerated repolarization, slightly increased the resting potential. In preparations depolarized partially by 26 mmol/l K+, both BMA (10(-4) mol/l) and IPR (10(-7) mol/l) induced slow response action potentials, but the duration of BMA-induced ones was twice longer than that of IPR-induced ones. BMA markedly reduced the 42K efflux from ventricular myocardium, whereas IPR had no effect on it. Moreover, BMA also decreased the 26 mmol/l K+-induced increment in 42K efflux, while IPR did not. It is concluded that BMA and IPR exert their positive inotropic effects on different ways. IPR increases the slow inward Ca2+ current directly by activating a phosphorylation process, whereas BMA enhances it indirectly by reducing the K+ conductance, lengthening the repolarization and consequently prolonging the time during which the slow inward Ca2+ current can be operative.     

Effects of Extracellular Diadenosine Tetraphosphate on Action Potentials in the Atrial and Ventricular Myocardium of the Rat Heart during Early Postnatal Ontogenesis

Diadenosine tetraphosphate (AP4A) belongs to a wide group of naturally derived endogenous purine compounds that have recently been considered as new neurotransmitters in the autonomic nervous system. It has been shown that AP4A induces inhibitory effects and modulates adrenergic control in the heart of adult mammals. Nevertheless, the physiological significance of AP4A in early postnatal development, when sympathetic innervation remains yet immature, has not been investigated. The aim of the present study was to elucidate the effects of AP4A on the heart bioelectrical activity in early postnatal ontogenesis. Action potentials (AP) were recorded using the standard microelectrode technique in multicellular isolated right atrial (RA), left atrial (LA), and ventricle (RV) preparations from male Wistar rats at postnatal days 1, 14, and 21 and from 60-day animals that were considered as adults. The application of AP4A caused significant reduction of AP duration in atrial (RA and LA) preparations from rats of all ages. Also, AP4A caused significant AP shortening in RV preparations from rats of various ages; however, the effect was more pronounced in 21-day-old and adult rats. AP4A failed to alter automaticity of RA preparations from the rats at postnatal days 1, 14, and 21 and weakly decreased spontaneous rhythm in RA preparations from the adult rats. The effect of AP4A was partially abolished by P2-receptor blocker PPADS in LA preparations from both 21-dayold and adult rats, while it failed to suppress AP4A-caused AP shortening in preparations from 1- and 14-dayold animals. Thus, extracellular AP4A causes shortening of AP both in the atrial and ventricular myocardium in the rats of early postnatal ontogenesis and in adults. The effect of AP4A depends on age only for ventricular myocardium where it may be attributed with growing contribution of diadenosine polyphosphates to the control of myocardium inotropy.     

Ionic mechanism of the Woodwors staircase

Analysis of single-chamber model of electromechanical coupling in the myocardial cell has shown that Woodwors staircase can be imitated in two cases: 1) stationary input current Ca2+ strongly exceeds the potential-dependent uptake of Ca2+ into the cell through the sarcolemma; 2) the action potential (AP) is shortened abruptly with an increase of the myocardium stimulation frequency. The experiments performed on a fragment of the frog heart ventricle supported the conclusions of the model. Blocking of Ca-channels with nifedipine (10(-6) g/mol) at the background of isotonic substitution of 70% of NaCl resulted in the development of "negative staircase" with an increase of stimulation rhythm. An abrupt shortening of AP after rest at joint action of adrenaline (10(-6) g/ml) and blocker of Ca-channels D-600 (10(-6) g/ml) was accompanied by Woodwors staircase.     

Mechanical function of hyoid muscles during spontaneous breathing in cats

We assessed the mechanical behavior of the geniohyoid and sternohyoid muscles during spontaneous breathing using sonomicrometry in anesthetized cats. When the animals breathed O2, the hyoid muscles either became longer or did not change length (but never shortened) during inspiration. During progressive hyperoxic hypercapnia, transient increases in geniohyoid muscle inspiratory lengthening occurred in many animals; however, at high PCO2 the geniohyoid invariably shortened during inspiration (mean 4.9% of resting length at the end of CO2 rebreathing; P less than 0.001). The PCO2 at which geniohyoid inspiratory lengthening changed to inspiratory shortening was significantly higher than the CO2 threshold for the onset of geniohyoid electrical activity (P less than 0.01). For the sternohyoid muscle, hypercapnia caused inspiratory lengthening in 13 of 17 cats and inspiratory shortening in 4 of 17 cats; on average the sternohyoid lengthened by 1.6% of resting length at the end of CO2 rebreathing (P less than 0.01). Sternohyoid lengthening occurred in spite of this muscle being electrically active. These results suggest that the relationship between hyoid muscle electrical activity and respiratory changes in length is very complex, so that the presence of hyoid muscle electrical activity does not necessarily indicate muscle shortening, and among the geniohyoid and sternohyoid muscles, the geniohyoid has a primary role as a hypopharyngeal dilator in the spontaneously breathing cat, with the sternohyoid muscle acting in an accessory capacity.     

Hystereses in the force-length relation and regulation of cross-bridge recruitment in tetanized rat trabeculae

Various mechanisms have been suggested to explain cardiac force-length Ca2+ relations. The existence of a cooperativity mechanism, whereby cross-bridge (XB) recruitment is affected by the number of active XBs, suggests that the force response to length oscillations should lag length oscillations. Consequently, the oscillatory force response should be larger during shortening than during lengthening. To test this prediction, force responses to large-sarcomere length (SL) oscillations (36.7 +/- 16.0 nm) at different SLs (n = 6) and frequencies (n = 7) were studied in intact tetanized trabeculae dissected from rat right ventricle (n = 13). Stable tetani were obtained by utilizing 30 microM cyclopiazonic acid in Krebs-Henseleit solution containing 6 mM extracellular Ca(2+) at 25 degrees C. SL was measured by laser diffraction techniques (Dalsa). Force was measured by silicone strain gauge. Instantaneous dynamic stiffness during large oscillations was measured by superimposing additional fast (50 or 200 Hz) and small-amplitude (2.25 +/- 0.25 nm) oscillations. The force responses lagged the SL oscillations at slow frequencies (112 +/- 41 ms at 1 Hz), and counterclockwise hystereses were obtained in the force-length plane: the force was higher during shortening than during lengthening. The delay in the force response decreased as the frequency of the SL oscillation was increased. Clockwise hysteresis, where the force preceded the SL, was obtained at frequencies >4 Hz. Similar hysteresis characteristics were obtained in the force-SL and stiffness-SL planes. Maximal lag was observed at the shortest SL, and the delay decreased with sarcomere elongation: 131.1 +/- 31.7 ms at 1.78 +/- 0.03 microm vs. 14.7 +/- 18.5 ms at 1.99 +/- 0.015 microm. The results establish the ability of cardiac fiber to adapt XB recruitment to changes in prevailing loading conditions. This study supports the stipulated existence of a cooperativity mechanism that regulates XB recruitment and highlights an additional method to characterize regulation of the force-length relation.     

Interspecies differences in the force-frequency relationship of the medial gastrocnemius motor units.

Single, functionally isolated motor units were studied in the medial gastrocnemius (MG) muscle of cats and rats. Axons of their motoneurons were stimulated with trains of pulses at frequencies increasing from 1 to 150 Hz and forces developed by muscle fibers were measured and force-frequency curves were compared between species. The following observations were made: (1) the most steep parts of curves (related to unfused tetani of motor units) begun at lower frequencies of stimulations in all types of feline motor units, (2) for fast motor units, the same relative values of force of unfused tetani were achieved at significantly lower frequencies of stimulations in the cat than in the rat. Twitch time parameters of both species influenced the course of force-frequency curves. It was showed that the contraction times of feline units varied in the wide range (21-81 ms), and these units reached 60% of the maximum force at stimulation frequencies between 10 and 38 Hz. On the other hand, contraction times of rat units ranged from 10 to 34 ms, whereas stimulation frequencies necessary to reach 60% of the maximum force varied considerably, from 12 to 65 Hz. The correlations between the above parameters were found for motor units of each species. However, the regression lines drown for the collected population of cat and rat units did not form linear continuity. Thus it seems that interspecies differences in the twitch contraction times do not fully explain different force-frequency relationships in mammalian skeletal muscles.     

Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3

In LQT3 patients, SCN5A mutations induce ultraslow inactivation of a small fraction of the hNav1.5 current, i.e. persistent Na⁺ current (I_pNa). We explored the time course of effects of such a change on the intracellular ionic homeostasis in a model of guinea-pig cardiac ventricular cell [Pasek, M., Simurda, J., Orchard, C.H., Christé, G., 2007b. A model of the guinea-pig ventricular cardiomyocyte incorporating a transverse–axial tubular system. Prog. Biophys. Mol. Biol., this issue]. Sudden addition of I_pNa prevented action potential (AP) repolarization when its conductance (g_pNa) exceeded 0.12% of the maximal conductance of fast I_Na (g_Na). With g_pNa at 0.1% g_Na, the AP duration at 90% repolarization (APD₉₀) was initially lengthened to 2.6-fold that in control. Under regular stimulation at 1 Hz it shortened progressively to 1.37-fold control APD₉₀, and intracellular [Na⁺]_i increased by 6% with a time constant of 106 s. Further increasing g_pNa to 0.2% g_Na caused an immediate increase in APD₉₀ to 5.7-fold that in control, which decreased to 2.2-fold that in control in 30 s stimulation at 1 Hz. At this time diastolic [Na⁺]_i and [Ca²⁺]_i were, respectively, 34% and 52% higher than in control and spontaneous erratic SR Ca release occurred.

In the presence of I_pNa causing 46% lengthening of APD₉₀, the model cell displayed arrhythmogenic behaviour when external [K⁺] was lowered to 5 mM from an initial value at 5.4 mM. By contrast, when K⁺ currents I_Kr and I_Ks were lowered in the model cell to produce the same lengthening of APD₉₀, no proarrhythmic behaviour was observed, even when external [K⁺] was lowered to 2.5 mM.     

Song pattern recognition in the grasshopper Chorthippus biguttulus: the mechanism of syllable onset and offset detection

The male song of the duetting grasshopper Chorthippus biguttulus consists of syllables alternating with noisy pauses. The syllable-pause structure is important for song recognition by the female. Using playback experiments we investigated the mechanism by which intensity modulations within the song pattern are used to detect syllable onsets and offsets. We varied the relative onset level (level of the syllable beginning relative to the noisy pause) and the relative offset level (level of the noisy pause relative to the syllable end) independently in different experiments. For all females, an increase in intensity defining the syllable onset was necessary to evoke responses. Syllable offset cues were not always necessary: some females responded to continuous noise stimuli wherein only syllable onsets were marked by short pulses of high intensity. Those females that did not require syllable offset cues did not, however, lack a functional pause detection mechanism, since their responses to model songs containing silent pauses were restricted to a given range of pause durations. We propose that syllable-pause detection involves two independent processes: (1) syllable onset detection by a phasic neuronal unit that can be re-activated only after a short pause, and (2) the rejection of unacceptably long pauses by a second unit.