Temperature effects on the Na and Ca currents in rat and hedgehog ventricular muscle

Cardiac transmembrane potentials and Na and Ca currents were recorded at different temperatures in rat and hedgehog ventricular muscle. At 35 degrees C in both species resting potential was about -80 mV and upstroke velocity (Vmax) of the action potential above 100 V/s. The shape of the action potential in hedgehog ventricular cells at 35 degrees C was similar to that in the rat showing a fast repolarization phase. When temperature was decreased, the membrane resting potential depolarized and action potential amplitude and Vmax declined. In rat ventricular cells at 10 degrees C, the resting potential was about -40 to -50 mV and Vmax was reduced to about 5 V/s. In hedgehog ventricular cells, however, the transmembrane potentials and Vmax were better maintained at low temperature. Phase 3 of the action potential was markedly prolonged below 20 degrees C in hedgehog but not in rat ventricular cells. When temperature was decreased to 10 degrees C the availability curve of the Na current shifted toward more negative potentials and ICa.peak declined in rat ventricular cells. In hedgehog cardiac preparations, the Na current was less influenced by the cooling and ICa.peak did not change very much at low temperatures. A transient inward current usually considered to induce cardiac arrhythmias could be recorded in rat ventricular cells below 20 degrees C but not in hedgehog preparations. These features of hedgehog cardiac membranes may contribute to the cold tolerance and the resistance to ventricular fibrillation during the hypothermia in mammalian hibernators.     

Effect of ouabain on mechanical and electrical properties of rat and guinea pig hearts at 180 C.

The effects of ouabain 10(-6) M on rat and guinea pig hearts have been studied at 18 degrees C, in order to reduce almost fully both the Na+, K+-dependent ATPase activity and the ouabain induced inhibition of this enzyme. In isolated guinea pig hearts the positive inotropic response to ouabain obtained at 32 degrees C disappeared at 18 degrees C. On the contrary, the contractile strength of rat hearts was slightly reduced by ouabain and in the same manner at both temperatures. Current and voltage clamp experiments carried out at 18 degrees C in ventricular fibres revealed that ouabain 10(-6) M decreased both the action potential overshoot and the fast sodium current in rat and guinea pig, by reduction of the membrane sodium conductance. Ouabain did not change the calcium current in guinea pig preparations, whereas in rat heart muscle this current was reduced. The effects of ouabain on both the action potential plateau and outward repolarizing current indicated some inconsistencies from preparation to preparation and cannot therefore be considered as significant. The persistence of the ouabain induced alterations of g Na (in rat and guinea pig) and calcium current (in rat) at 18 degrees C supports the hypothesis of two ouabain cell receptors in heart muscle.     

Transmembrane electrical characteristics of cultured human skeletal muscle cells

Skeletal muscle explants from normal subjects were established from biopsy material on collagen. Cellular outgrowth appeared within 3-4 days, and fusion of myoblasts was observed in 5-10 days. Multinucleated myotubes were impaled under high optical magnification, at 37 degrees C, with conventional glass microelectrodes. The mean resting potential was -44.4 mV +/- 2.4 (n = 399); -33 +/- 2.3 mV at 9 days (n = 10) vs -48 +/- 2.5 mV (n = 15) at 27 days. The average input resistance (Rin) was 9.7 M omega (n = 83). Action potentials could be elicited by electrical stimulation and had a mean amplitude of 55.9 +/- 2.1 mV with a mean maximum rate of rise (Vmax) of 72.1 +/- 7.5 V/s. The mean overshoot was 13.9 +/- 2.3 mV, and the action potential duration determined at 50% of repolarization (APD50) was 8.0 msec (n = 7). The resting membrane potential showed a depolarization of 23 mV/decade for extracellular potassium ion concentration ([K]o) between 4.5-100 mM. Thus, we have established the normal resting potential and maximum rate of rise of the action potential for human myotubes in culture. We have shown that the values for these are less than those previously reported in cultured avian and rodent cells. In addition, we have shown that the response in our system of the resting potential to change in extracellular potassium concentration is blunted compared to studies using isolated muscle, suggesting an increase in ratio of sodium to potassium permeability. Cultured human muscle cells depolarized in the presence of ouabain.     

Lysis of tumor cells by antibody and complement. VI. Enhanced killing of enzyme-pretreated tumor cells.

The ascites form of a chemically induced guinea pig hepatoma, line-10, was resistant to killing in vitro by xenogeneic antibody and guinea pig complement. Pretreatment of line-10 cells with certain proteolytic enzymes rendered tham susceptible to the killing action of antibody and guinea pig complement. The effects of enzyme pretreatment were dependent on enzyme concentration, temperature, and could be blocked by addition of competitive or non-competitive inhibitors. The effect of the enzyme treatment could reversed by incubating the treated cells at 37 degrees C (but not at 0 degrees C), in the absence of the enzyme. Effective enzymes included ficin, bromelain, pronase, elastase, papain, trypsin, collagenase, lipases type I and type VI, and the neuraminidase preparation isolated from Clostridium perfringens. The activity of the lipase preparations and the neuraminidase preparation isolated from Clostridium perfringens appeared to be caused by proteolytic enzyme contamination. Enzyme preparations that proved ineffecitve in rendering the line-10 cells sensitive to killing by antibody and guinea pig complement included DNase, RNase, beta-glucuronidase type 6A or type B10, hyaluronidase type V or type VI, and pectinesterase.     

Temperature dependence of the maternal-fetal electrical potential difference in guinea pigs

An electrical potential difference (PD) is measured between maternal organism and fetus in the pregnant guinea pig. To investigate whether the PD is generated by active or passive forces these studies examined the temperature dependence of the PD in guinea pigs at 55-61 days gestation. Anesthesia was induced (ketamine, 44 mg/kg) and maintained (halothane, 1.5%) in 5 pregnant guinea pigs. The animals were subjected to alternating 1 hour periods of cooling and recovery, changing core body and intrauterine temperature about 5 degrees C. PD was monitored continuously with Ag/AgCl electrodes placed in the maternal abdominal cavity and the amniotic fluid. The resting PD (+/- SEM) was 24.1 +/- 2.8 mV. Analysis of covariance indicated that PD decreased slowly with time and increased significantly with lowered temperature. A second group of 4 guinea pigs was studied after beta blockade with propranolol (0.1 mg iv, repeated hourly). In this group the resting PD was 20.7 +/- 3.6 mV. The PD decreased gradually with time and decreased consistently during cooling. In the propranolol group the relation between PD and temperature yielded a calculated activation energy of 11.7 +/- 0.8 kcal/mol (Q10 = 1.9, 30-40 degrees C). These results are consistent with the hypothesis that at least some of the PD is generated by an energy-dependent electrogenic ion pump, or by selective passive diffusion of ions across a lipid membrane during which a significant energy barrier is overcome. They are not consistent with the generation of the PD exclusively by passive streaming of ions through water-filled channels. During cooling catecholamines are presumably released, favoring the generation of the PD.     

Electrophysiological and pharmacological evidence that peripheral type benzodiazepine receptors are coupled to calcium channels in the heart

PK 11195, an antagonist of the peripheral type benzodiazepine receptor, does not affect either the duration of the action potential or the tension of the guinea pig papillary muscle. However, it antagonized the effects of the calcium channel blockers, nitrendipine, verapamil, diltiazem, and of BAY K8644, a calcium channel agonist in this heart preparation. On the other hand, PK 11195 does not change the increase in the action potential duration provoked by the potassium channel blocker tetraethylammonium. RO5-4864, an agonist of the peripheral type benzodiazepine receptor, decreased the tension of the guinea pig papillary muscle. The effect was reversed by increasing extracellular Ca2+ concentrations up to 4 mM. These results suggest that in the heart the peripheral type benzodiazepine receptors are coupled to calcium channels.     

Characteristics of the functional properties of the spinal cord motoneurons of old rats]

The mean membrane potential (MP) of old rats did not differ significantly from that in young mature rats ((58.4 +/- +/-1,4 mV and 56.6 +/- 1.26 mV, respectively). At the same time the frequency of detection of motor neurons with the MP OF 70 mV and more fell by 18.6%, and with the MP of 50-59 mV -increased by 14.2% in the old, in comparison with the young animals. The direct excitability threshold in old rats decreased (3.0 +/- 3-10(-9) in young mature and 2.0 +/- 0.2-10(-9) a in old rats; P less than 0.02). The number of discharges per 50 msec of the neuron poliarization reached 4-5, constituting 80-100 pulse/min. When determined by the first two intervals the action potential frequency reached 125 pulse/sec, and in the young mature rats--over 300 pulse/sec. The duration of antidromic spikes was increased (1.02 +/- 0.09 msec in young mature animals and 1.65 +/- 0.14 msec in the old animals; P less than 0.001). The antidromic spikes of the neurons in old mature rats, as a rule, had no delayed depolarization.     

Effect of a new beta-blocker (CM 6805) on the action potential of guinea pig atrial fiber

CM6804 effect has been studied about some parameters of the intracellular action potential (AP) of guinea pig autorythmic auricle. Auricle was preserved alive under Tyrode oxygenated solution at 37 degrees C. AP is measured by a fluctuating intracellular glass microelectrode. At a concentration of 5 . 10(-5) M, CM doesn't alter the resting membrane potential, it causes a small overshoot reduction, it decreases the maximum depolarization rate and the heart rate, it increases the action potential duration. Overshoot and maximum depolarization rate decrease prove that CM modifies the membrane permeability probably by a diminution of the sodium rapid inward current. CM action is similar to others aryl-oxy-propyl propanolamine like propranolol.     

Temperature-sensitive gating of cation current in guinea pig ileal muscle activated by hyperpolarization

The temperature dependence of hyperpolarization-activated current (I(h)) was investigated in freshly isolated guinea pig ileal smooth muscle cells, using the nystatin-perforated whole cell recording technique. Hyperpolarizing pulses (-50 to -120 mV) from -40 mV evoked time-dependent inward rectifying currents with a reversal potential of -33 mV and a slow activation time course well approximated by a single exponential. The properties of these currents, such as steady-state variables, dependence on external K, modification by norepinephrine, and blockade by Cs or ZD-7288, coincide well with those of the "classical" I(h) discovered in the sinoatrial node. Raising the temperature (range: 22-33 degrees C) accelerated the activation time course of this I(h) and shifted its 50% activation potential positively (12 mV/10 degree) with much less change in the maximum conductance. Based on a simple closed-open model, this can be explained by a high temperature dependence of the opening rate constant (temperature coefficient: 3.4). The activation profile of reconstructed I(h) at 36 degrees C suggests that a considerable overlap could occur between the ranges of I(h) activation and physiological membrane potential.     

The electrophysiological and mechanical effects of atrial natriuretic peptide and acetylcholine on guinea pig ventricular papillary muscle

The direct effects of atrial natriuretic factor (ANF) and acetylcholine (ACh) on isolated guinea pig ventricular papillary muscle were studied. ANF (3 x 10(-9) - 3 x 10(-7) M), a cardiogenic hormone, had no significant electrical or mechanical effects on guinea pig papillary muscle driven at a frequency of 60 beats/min in normal (4 mM) and high [K]0 (27 mM) Tyrode solutions. On the other hand, ACh (3 x 10(-8) - 3 x 10(-7) M) caused a significant shortening of action potential duration and the contractile force showed no change or a slight decrease. At high concentration (5 microM), ACh reduced action potential durations at 50% and 90% repolarization (APD50 and APD90) by 10.5 +/- 2.1% and 12.4 +/- 1.8%, respectively, but the contractile force was slightly increased by 9.8 +/- 1.2%. In eleven of twenty-six preparations, spontaneous activity occurred and intermingled with driven activity. The ectopic rhythms were suppressed by ACh (1-5 microM). The changes in electrical but not mechanic activity induced by ACh were suppressed in the presence of five micromolar atropine. These results reveal that, in guinea pig papillary muscle, ANF had no direct chronotropic or inotropic effect. ACh may reduce APD and spontaneous discharges through an activation of muscarinic receptors but enhance twitch tension through other mechanisms.     

The initial inward current in spherical clusters of chick embryonic heart cells

The rapid inward sodium current in spherical clusters of 11-d-old embryonic chick heart cells, ranging in size between 65 and 90 micron diameter, was studied using the two-microelectrode voltage-clamp technique. Using these preparations, it was possible to resolve the activation phase of the rapid inward current for potentials negative to -25 mV at 37 degrees C. The rapid inward current exhibited a voltage and time dependence similar to that observed in other excitable tissues. It was initiated at potential steps more positive than -45 mV. The magnitude of the current reached its maximum value at a potential of approximately -20 mV. The measured reversal potential was that predicted by the Nernst equation for sodium ions. The falling phase of the current followed a single exponential time-course with a time constant of inactivation, tau h, ranging between 2.14 ms at -40 mV and 0.18 ms at -5 mV. The time constant of inactivation, tau h, determined by a single voltage-step protocol was compared to the constant, tau c, determined by a double voltage-step protocol and no significant different between the two constants of inactivation was found. Furthermore, the time constants of inactivation and reactivation at the same potential in the same preparation were similar. The results of this study demonstrate that the sodium current of heart cells recorded at 37 degrees C can be described by Hodgkin-Huxley kinetics with speeds approximately four times faster than the squid giant axon at 15 degrees C.     

慢性低氧对豚鼠右室心肌细胞钙、钾电流的影响

采用全细胞膜片箝技术,分别记录并比较正常对照组与慢性低氧组豚鼠单个右室心肌细胞的膜电容、L型钙电流和延迟整流钾电流峰值和电流-电压关系曲线,以探讨慢性低氧对豚鼠右室心肌细胞L型钙电流和延迟整流钾电流的影响。结果表明,上述两组细胞膜电容分别为（155±13．2）pF、（179±14,8）pF,低氧组显著大于正常对照组（P＜0．01）;L型钙电流峰值分别为（1．07±0．21）nA和（0．99±0．17）nA,两组之间无显著差异;在-20mV至＋20mV,慢性低氧组L型钙电流密度较正常对照组显著下降（P＜0．05）。在＋月mV至＋60mV之间,慢性低氧组豚鼠右室心肌细胞延迟整流钾电流幅度均小于正常对照组;在-20mV至＋60mV之间,慢性低氧组豚鼠右室心肌细胞延迟整流钾电流密度明显低于正常对照组。可见慢性低氧能使豚鼠右室心肌细胞膜电容增加,L型钙电流幅度不变,但L型钙电流密度下降;同时慢性低氧降低豚鼠右室心肌细胞延迟整流钾电流幅度和密度。     

Hypothermia increases the gain of excitation-contraction coupling in guinea pig ventricular myocytes

Components of excitation-contraction (EC)-coupling were compared at 37 degrees C and 22 degrees C to determine whether hypothermia altered the gain of EC coupling in guinea pig ventricular myocytes. Ca(2+) concentration (fura-2) and cell shortening (edge detector) were measured simultaneously. Hypothermia increased fractional shortening (8.3 +/- 1.7 vs. 2.6 +/- 0.3% at 37 degrees C), Ca(2+) transients (157 +/- 33 vs. 35 +/- 5 nM at 37 degrees C), and diastolic Ca(2+) (100 +/- 9 vs. 60 +/- 6 nM at 37 degrees C) in field-stimulated myocytes (2 Hz). In experiments with high-resistance microelectrodes, the increase in contractions and Ca(2+) transients was accompanied by a twofold increase in action potential duration (APD). When voltage-clamp steps eliminated changes in APD, cooling still increased contractions and Ca(2+) transients. Hypothermia increased sarcoplasmic reticulum (SR) Ca(2+) stores (83 +/- 17 at 37 degrees C to 212 +/- 50 nM, assessed with caffeine) and increased fractional SR Ca(2+) release twofold. In contrast, peak Ca(2+) current was much smaller at 22 degrees C than at 37 degrees C (1.3 +/- 0.4 and 3.5 +/- 0.7 pA/pF, respectively). In cells dialyzed with sodium-free pipette solutions to inhibit Ca(2+) influx via reverse-mode Na(+)/Ca(2+) exchange, hypothermia still increased contractions, Ca(2+) transients, SR stores, and fractional release but decreased the amplitude of Ca(2+) current. The rate of SR Ca(2+) release per unit Ca(2+) current, a measure of EC-coupling gain, was increased sixfold by hypothermia. This increase in gain occurred regardless of whether cells were dialyzed with sodium-free solutions. Thus an increase in EC-coupling gain contributes importantly to positive inotropic effects of hypothermia in the heart.     

Regulation of action potential duration under acute heat stress by I(K,ATP) and I(K1) in fish cardiac myocytes

The mechanism underlying temperature-dependent shortening of action potential (AP) duration was examined in the fish (Carassius carassius L.) heart ventricle. Acute temperature change from +5 to +18 degrees C (heat stress) shortened AP duration from 2.8 +/- 0.3 to 1.3 +/- 0.1 s in intact ventricles. In 56% (18 of 32) of enzymatically isolated myocytes, heat stress also induced reversible opening of ATP-sensitive K+ channels and increased their single-channel conductance from 37 +/- 12 pS at +8 degrees C to 51 +/- 13 pS at +18 degrees C (Q10 = 1.38) (P < 0.01; n = 12). The ATP-sensitive K+ channels of the crucian carp ventricle were characterized by very low affinity to ATP both at +8 degrees C [concentration of Tris-ATP that produces half-maximal inhibition of the channel (K1/2)= 1.35 mM] and +18 degrees C (K1/2 = 1.85 mM). Although acute heat stress induced ATP-sensitive K+ current (IK,ATP) in patch-clamped myocytes, similar heat stress did not cause any glibenclamide (10 microM)-sensitive changes in AP duration in multicellular ventricular preparations. Examination of APs and K+ currents from the same myocytes by alternate recording under current-clamp and voltage-clamp modes revealed that changes in AP duration were closely correlated with temperature-specific changes in the voltage-dependent rectification of the background inward rectifier K+ current IK1. In approximately 15% of myocytes (4 out of 27), IK,ATP-dependent shortening of AP followed the IK1-induced AP shortening. Thus heat stress-induced shortening of AP duration in crucian carp ventricle is primarily dependent on IK1. IK,ATP is induced only in response to prolonged temperature elevation or perhaps in the presence of additional stressors.     

Phenotypic effects of thermal mean and fluctuations on embryonic development and hatchling traits in a lacertid lizard, Takydromus septentrionalis

How fluctuating temperatures influence reptilian embryos and hatchlings has attracted increasing scientific attention, but is poorly known. We conducted an incubation experiment with a factorial design of two mean temperatures (24 vs. 28 degrees C) and three diel thermal fluctuations (0, +/-3, +/-6 degrees C) to determine the effects of diel thermal fluctuations and mean temperature on incubation duration and hatchling phenotypes. Both diel thermal fluctuations and mean temperature significantly affected incubation duration, but not hatching success. Incubation duration increased with increasing temperature fluctuations at a mean temperature of 24 degrees C, but not at a mean temperature of 28 degrees C. The significant interaction between diel thermal fluctuations and mean temperature on hatchling morphology indicated that the effect of thermal fluctuations depended on the mean temperature. Hatchling mass differed significantly between 24+/-6 and 28+/-6 degrees C, but not between the two constant temperatures or the temperatures with +/-3 degrees C fluctuations. At a mean temperature of 24 degrees C, the effect of thermal fluctuations on hatchling size was marginally significant, with relatively large hatchlings at the constant temperature; at a mean temperature of 28 degrees C, thermal fluctuations had no impact on hatchling size. The locomotor performances were significantly affected by mean temperature rather than diel thermal fluctuations. Therefore, diel thermal fluctuations around a given mean temperature do not affect hatchling phenotypes in a relatively large magnitude, but the influence of diel thermal fluctuations may differ with changing mean temperatures.     

Effect of thymol on calcium handling in mammalian ventricular myocardium

Concentration-dependent effects of thymol on calcium handling were studied in canine and guinea pig cardiac preparations (Langendorff-perfused guinea pig hearts, canine ventricular trabeculae, canine sarcoplasmic reticular vesicles and single ryanodine receptors). Thymol induced a concentration-dependent negative inotropic action in both canine and guinea pig preparations (EC(50) = 297 +/- 12 microM in dog). However, low concentrations of thymol reduced intracellular calcium transients in guinea pig hearts without decreasing contractility. At higher concentrations both calcium transients and contractions were suppressed. In canine sarcoplasmic reticular vesicles thymol induced rapid release of calcium (V(max) = 0.47 +/- 0.04 nmol s(-1), EC(50) = 258 +/- 21 microM, Hill coefficient = 3.0 +/- 0.54), and decreased the activity of the calcium pump (EC(50) = 253 +/- 4.7 microM, Hill coefficient = 1.62 +/- 0.05). Due to the less sharp concentration-dependence of the ATPase inhibition, this effect was significant from 50 microM, whereas the thymol-induced calcium release only from 100 microM. In single ryanodine receptors incorporated into artificial lipid bilayer thymol induced long lasting openings, having mean open times increased with 3 orders of magnitude, however, the specific conductance of the channel remained unaltered. This effect of thymol was not voltage-dependent and failed to prevent the binding of ryanodine. In conclusion, the negative inotropic action of thymol can be explained by reduction in calcium content of the sarcoplasmic reticulum due to the combination of the thymol-induced calcium release and inhibition of the calcium pump. The calcium-sensitizer effect, observed at lower thymol concentrations, indicates that thymol is likely to interact with the contractile machinery also.     

Beta-adrenergic modulation of cardiac ion channels. Differential temperature sensitivity of potassium and calcium currents

beta-Adrenergic stimulation of ventricular heart cells results in the enhancement of two important ion currents that regulate the plateau phase of the action potential: the delayed rectifier potassium channel current (IK) and L-type calcium channel current (ICa). The temperature dependence of beta-adrenergic modulation of these two currents was examined in patch-clamped guinea pig ventricular myocytes at various steps in the beta-receptor/cyclic AMP-dependent protein kinase pathway. External applications of isoproterenol and forskolin were used to activate the beta-receptor and the enzyme adenylate cyclase, respectively. Internal dialysis of cyclic 3',5'-adenosine monophosphate (cAMP) or the catalytic subunit of cAMP-dependent protein kinase (CS), as well as the external addition of 8-chlorphenylthio cAMP (CPT-cAMP) was applied to increase intracellular levels of cAMP and CS. Isoproterenol-mediated increases in IK, but not ICa, were found to be very temperature dependent over the range of 20-37 degrees C. At room temperature (20-22 degrees C) isoproterenol produced a large (threefold) enhancement of ICa but had no effect on IK. In contrast, at warmer temperatures (30-37 degrees C) both currents increased in the presence of this agonist and the kinetics of IK were slowed at -30 mV. A similar temperature sensitivity also existed after exposure to forskolin, CPT-cAMP, cAMP, and CS, suggesting that this temperature sensitivity of IK may arise at the channel protein level. Modulation of IK during each of these interventions was accompanied by a slowing in IK kinetics. Thus, regulation of cardiac potassium channels but not calcium channels involves a temperature-dependent step that occurs after activation of the catalytic subunit of cAMP-dependent protein kinase.     

Electrophysiological effects of the aqueous extract of Averrhoa carambola L. leaves on the guinea pig heart

This work aims to describe some electrophysiological changes promoted by the aqueous extract (AEx) from Averrhoa carambola leaves in guinea pig heart. The experiments were carried out on isolated heart or on right atrium-ventricle preparations. In 6 hearts, the extract induced many kinds of atrioventricular blocks (1st, 2nd, and 3rd degrees); increased the QT interval from 229+/-23 to 264+/-19 ms; increased the QRS complex duration from 27+/-3.1 to 59+/-11 ms, and depressed the cardiac rate from 136+/-17 to 89+/-14b pm. Furthermore, it decreased the conduction velocity of atrial impulse (17+/-3%); reduced the intraventricular pressure (86+/-6%), and increased the conduction time between the right atrium and the His bundle (27+/-6.5%). The conduction time from the His bundle to the right ventricle was not altered. Atropine sulfate did not change either the electrocardiographic parameters or the intraventricular pressure effects promoted by the A. carambola AEx. Based on these results, the popular use of such extracts should be avoided because it can promote electrical and mechanical changes in the normal heart.     

Myocardial infarction in the guinea pig: cellular electrophysiology

The cellular electrophysiology of left ventricular preparations from guinea pig hearts was studied 1 hour, 24 hours, and 4-6 weeks after myocardial infarction produced by 6-8 single ties of the distal left coronary artery system or after sham operation. Microelectrode recordings were used to monitor cells from the endocardial surface of each preparation in tissue bath. All coronary ligated preparations displayed accelerated spontaneous activity compared to normal and sham operated preparations. Single and multiple premature ventricular depolarizations occurred frequently in coronary ligated and rarely in normal and sham operated preparations. Premature stimuli delivered to areas overlying and bordering the area of infarction, induced short bursts of self-terminating rapid repetitive ventricular activity in 4 of 8 (50%) acute (1-hour), 5 of 9 (55%) subacute (24-hour), and 14 of 20 (70%) healed (4-6-week) infarcted preparations. Such activity could not be induced in normal and sham operated preparations. The preparations with healed infarction were unique in that they demonstrated runs of self-terminating repetitive ventricular activity which occurred spontaneously or was inducible with premature stimulation. Recordings from multiple sites in acute, subacute, and healed preparations revealed a variety of transmembrane action potential abnormalities (i.e., reduced action potential amplitude and resting potential, decreased and increased action potential duration, and depressed maximum rates of phase 0 depolarization) in cells overlying and bordering areas of infarction. Only Purkinje fiber action potentials were recorded over the healed infarcts. These data demonstrate that a spectrum of electrophysiological alterations occur in response to ischemic injury and persist after healing of the injury in this new model of myocardial infarction utilizing the guinea pig.     

Comparative aspects and temperature dependence of [3H]1,4-dihydropyridine Ca2+ channel antagonist and activator binding to neuronal and muscle membranes

Binding of [3H]nitrendipine, [3H]nimodipine, and (+)[3H]PN 200-110 to microsomal preparations of guinea pig smooth and cardiac muscle and brain synaptosomes revealed high affinity interaction with KD values in the sequence, (+)PN 200-110 greater than nitrendipine greater than nimodipine. Bmax values for a particular tissue were independent of the 1,4-dihydropyridine employed in radioligand binding at 25 degrees C. The temperature dependence of [3H]nitrendipine binding in cardiac and smooth muscle microsomal preparations and brain synaptosomes was measured from 0 degrees to 37 degrees C and for skeletal muscle preparations from 0 degrees to 30 degrees C. Bmax values increased with temperature for cardiac membranes, but did not vary in other tissues. van't Hoff plots were nonlinear in all tissues, enthalpy and entropy changes becoming increasingly negative with increasing temperature. Competition binding of the activator-antagonist enantiomeric 1,4-dihydropyridine pairs of Bay k 8644 and PN 202-791 for [3H]nitrendipine in smooth muscle did not reveal significant thermodynamic differences between activator and antagonist molecules.