Cardiac electric field at the period of depolarization and repolarization of the frog heart ventricle

Multichannel mapping of electrical field on heart ventricle epicardium and the body surface in frogs Rana esculenta and Rana temporaria was performed at periods of the ventricular myocardium depolarization and repolarization. The zone of the epicardium early depolarization is located on epicardium of the ventricle base posterior wall, while the late depolarization zone—on its apex and on the base anterior wall. The total vector of sequence of the ventricle epicardium depolarization is directed from the base to the apex. The zone of the early repolarization is located in the apical area, while that of the late one—in the area of the base. On the frog body surface the cardioelectric field with the cranial zone of negative and the caudal zone of positive potentials is formed before the appearance of the QRS complex on ECG. At the period of the heart ventricle repolarization the zone of the cardioelectric field negative potentials is located in the cranial, while that of the positive ones—in the body surface caudal parts. The cardioelectric field on the frog body surface at the periods of depolarization and repolarization of the ventricle myocardium reflects adequately the projection of sequence of involvement with excitation and of distribution of potentials on epicardium.     

Cardiac electric field at the period of depolarization and repolarization of the frog heart ventricle

Multichannel mapping of electrical field on heart ventricle epicardium and the body surface in frogs Rana esculenta and Rana temporaria was performed at periods of the ventricular myocardium depolarization and repolarization. The zone of the epicardium early depolarization is located on epicardium of the ventricle base posterior wall, while the late depolarization zone--on its apex and on the base anterior wall. The total vector of sequence of the ventricle epicardium depolarization is directed from the base to the apex. The zone of the early repolarization is located in the apical area, while that of the late one--in the area of the base. On the frog body surface the cardioelectric field with the cranial zone of negative and the caudal zone of positive potentials is formed before the appearance of the QRS complex on ECG. At the period of the heart ventricle repolarization the zone of the cardioelectric field negative potentials is located in the cranial, while that of the positive ones--in the body surface caudal parts. The cardioelectric field on the frog body surface at the periods of depolarization and repolarization of the ventricle myocardium reflects adequately the projection of sequence of involvement with excitation and of distribution of potentials on epicardium.     

Cardiac electric field on the epicardial and body surfaces during the period of depolarization and repolarization of ventricular myocardium in pikes

Body surface and ventricular epicardial potential distributions during the electrocardiographic QRST interval were studied in pikes with the aid of potential mapping. The earliest epicardial activation was observed at the posterior base near the atrioventricular orifice. The areas of the earliest repolarization were found at the apex and the posterior base, whereas the area of the latest repolarization was detected at the anterior base. In the initial period of the QRS, the minimum was developed in the middle third of the right lateral body surface, and the maximum in the middle third of the ventral body surface. The body surface potential distribution during the ST-Twas characterized by the clear-cut negative potential zone in the cranial ventral area with the rest of the body surface having positive potentials, a pattern being largely unchanged throughout the period of the T-wave. The ventricular epicardial repolarization sequence differed from the activation sequence. The ventricular epicardial depolarization and repolarization sequences as well as epicardial potential distributions are expressed in the cardiac electric field on the body surface during the QRS and ST-T complexes.     

Temperature-dependent inotropic action of A23187 on guinea-pig ventricular muscles

The effects of the Ca2+ ionophore, A23187, on the contraction and membrane action potential of the isolated guinea-pig papillary muscle were examined at various temperatures (30-16 degrees C) and compared to those of isoprenaline and a high calcium medium. A23187 caused a marked positive inotropic effect with a significant prolongation of the action potential duration at an early repolarization phase but not a late repolarization phase at normal temperature (30 degrees C). Such an inotropic effect was completely abolished at low temperature (16 degrees C) where a marked positive inotropic effect of isoprenaline (5 X 10(-8) M) and a high calcium medium (6.2 mM) still remained. These results suggest that the cardiac responsiveness to A23187 was sensitive to a low temperature at which a membrane lipid phase transition may occur.     

A novel mutation (T65P) in the PAS domain of the human potassium channel HERG results in the long QT syndrome by trafficking deficiency

The congenital long QT syndrome is a cardiac disease characterized by an increased susceptibility to ventricular arrhythmias. The clinical hallmark is a prolongation of the QT interval, which reflects a delay in repolarization caused by mutations in cardiac ion channel genes. Mutations in the HERG (human ether-à-go-go-related gene KCNH2 can cause a reduction in I(Kr), one of the currents responsible for cardiac repolarization. We describe the identification and characterization of a novel missense mutation T65P in the PAS (Per-Arnt-Sim) domain of HERG, resulting in defective trafficking of the protein to the cell membrane. Defective folding of the mutant protein could be restored by decreased cell incubation temperature and pharmacologically by cisapride and E-4031. When trafficking was restored by growing cells at 27 degrees C, the kinetics of the mutated channel resembled that of wild-type channels although the rate of activation, deactivation, and recovery from inactivation were accelerated. No positive evidence for the formation of heterotetramers was obtained by co-expression of wild-type with mutant subunits at 37 degrees C. As a consequence the clinical symptoms may be explained rather by haploinsufficiency than by dominant negative effects. This study is the first to relate a PAS domain mutation in HERG to a trafficking deficiency at body temperature, apart from effects on channel deactivation.     

Cardioelectric Field on the Bird Body Surface during Activation of Atrial Myocardium

Cardioelectric field (CEF) on the body surface of birds (hen and pigeon) at the period of atrial excitation was studied by the method of the 64-channel synchronous electrocardiotopography. At the period of the atrial depolarization in the birds the zone of CEF negative potentials on the body surface is located cranially with respect to the zone of positive potentials. At the initial moments of P wave the minimum is located in the cranial (hen) or middle (pigeon) third of the dorsal body surface, while the maximum—in the area of the heart projection onto the ventral (hen) or left-lateral (pigeon) body surface. The maximum and minimum of the potential reach the greatest value at the period of the middle part of the P wave (near the peak), their amplitude being higher in pigeons. The distribution dynamics of the CEF potentials on the body surface is similar in different bird species and is characterized by stability in mutual disposition of positive and negative zones. The interspecies and intraspecies CEF variability on the body surface at the period of the atrial activation seems to be due to differences in the heart disposition in the chest. At the period of the atrial myocardium activation, CEF on the bird body surface reflects adequately projection of the potential distribution on epicardium and the sequence of spreading of excitation in the atrial myocardium, including that in the presence of several fronts of depolarization waves.     

Effect of hypothermia on sequence of the ventricle epicardium repolarization in rabbits]

In anaesthetised rabbits at normal body temperature, the earliest ventricles' epicardial recovery occurs at the heart apex and adjacent left ventricle's surface whereas the latest one occurs at the epicardium of the right ventricle's base. A decrease in the mediastinum temperature to 32 degrees C reversed the recovery sequence. Following the cooling of the heart, the longest prolongation of the activation-recovery interval occurred at the heart apex area and the lowest one--at the right ventricle base.     

Hyperthermia and neural tube defects of the curly-tail mouse

The mutant gene curly-tail produces neural tube defects (NTD) in 60% of mice, predominantly at the caudal end of the neural tube. Only 1% of individuals have exencephaly. Pregnant curly-tail mice and C57BL mice which are not genetically pre-disposed to NTD, were subjected to various regimes of hyperthermia on day 8 or on day 9 or on day 10 of gestation. Normal body temperature was around 36.8 degrees C, but it was found to be extremely labile in response to heat exposure. It was significantly raised for 15 min of a 20-min exposure period, and, after removal from the heat, it dropped rapidly. In C57BL mice, heat treatment produced exencephaly alone and in only 3% of mice. In curly-tail mice, none of the heat-treatment regimes had any consistent effect on the incidence of posterior NTD but produced specifically exencephaly. The incidence was increased slightly at an environmental temperature of 37 degrees C when the body temperature was 4.01 degrees C; at an ambient temperature of 43 degrees C and a body temperature of 42 degrees C, the incidence of exencephaly was 20%. Exencephaly was produced by two periods of 20 min heat exposures 7 hr apart or a single exposure of 1 hr, especially on day 8 of gestation, but not by a single 20 min exposure. It is concluded that these experiments, performed in a mutant predisposed to lesions especially at the caudal end of the neural tube, demonstrate the specificity of hyperthermia for affecting closure of the cranial neural folds.     

Rapid mechanical and thermal changes in the garfish olfactory nerve associated with a propagated impulse.

Mechanical and thermal changes associated with a propagated nerve impulse were determined using the garfish olfactory nerve. Production of an action potential was found to be accompanied by swelling of the nerve fibers. The swelling starts nearly at the onset of the action potential and reaches its peak at the peak of the action potential. There is a decrease in the length of the fibers while an impulse travels along the fibers. The time-course of the initial heat was determined at room temperature using heat-sensors with a response-time of 2-3 ms. Positive heat production was found to start and reach its peak nearly simultaneously with the action potential. The rise in temperature of the nerve was shown to be 23 (+/- 4) mu degrees C. In the range between 10 degrees and 20 degrees C, the temperature coefficient of heat production is negative, primarily due to prolongation of the period of positive heat production at low temperatures. The amount of heat absorbed during the negative phase varies widely between 45 and 85% of the heat evolved during the positive phase. It is suggested that both mechanical and thermal changes in the nerve fibers are associated with the release and re-binding of Ca-ions in the nerve associated with action potential production.     

Impact of Hypokalemia on Electromechanical Window,Excitation Wavelength and Repolarization Gradients in Guinea-Pig and Rabbit Hearts

Normal hearts exhibit a positive time difference between the end of ventricular contraction and the end of QT interval, which is referred to as the electromechanical (EM) window. Drug-induced prolongation of repolarization may lead to the negative EM window, which was proposed to be a novel proarrhythmic marker. This study examined whether abnormal changes in the EM window may account for arrhythmogenic effects produced by hypokalemia. Left ventricular pressure, electrocardiogram, and epicardial monophasic action potentials were recorded in perfused hearts from guinea-pig and rabbit. Hypokalemia (2.5 mM K⁺) was found to prolong repolarization, reduce the EM window, and promote tachyarrhythmia. Nevertheless, during both regular pacing and extrasystolic excitation, the increased QT interval invariably remained shorter than the duration of mechanical systole, thus yielding positive EM window values. Hypokalemia-induced arrhythmogenicity was associated with slowed ventricular conduction, and shortened effective refractory periods, which translated to a reduced excitation wavelength index. Hypokalemia also evoked non-uniform prolongation of action potential duration in distinct epicardial regions, which resulted in increased spatial variability in the repolarization time. These findings suggest that arrhythmogenic effects of hypokalemia are not accounted for by the negative EM window, and are rather attributed to abnormal changes in ventricular conduction times, refractoriness, excitation wavelength, and spatial repolarization gradients.     

The contribution of ventricular apicobasal and transmural repolarization patterns to the development of the T wave body surface potentials in frogs (Rana temporaria) and pike (Esox lucius)

The study aimed at the simultaneous determination of the transmural and apicobasal differences in the repolarization timing and the comparison of the contributions of these two repolarization gradients to the development of the body surface T wave potentials in animals with the single heart ventricle (fishes and amphibians). Unipolar potentials were measured on the body surface, epicardium and in the intramural (subepicardial, Epi; midmyocardial; and subendocardial, Endo) ventricular layers of 9 pike and 8 frogs. Activation times, repolarization times and activation-recovery intervals were determined. A transmural gradient in repolarization durations in frogs (Endo>Epi, P<0.024) corresponds to the gradient in repolarization times. No significant transmural difference in repolarization duration is observed in pike that produces a repolarization sequence from Endo to Epi (Endo相似文献   

Temperature Dependence of Pyrethroid Modification of Single Sodium Channels in Rat Hippocampal Neurons

Pyrethroid modulation of sodium channels is unique in the sense that it is highly dependent on temperature, the potency being augmented by lowering the temperature. To elucidate the mechanisms underlying the negative temperature dependence of pyrethroid action, single sodium channel currents were recorded from cultured rat hippocampal neurons using the inside-out configuration of patch-clamp technique, and the effects of the pyrethroid tetramethrin were compared at 22 and 12°C. Tetramethrin-modified sodium channels opened with short closures and/or transitions to subconductance levels at 22 and 12°C. The time constants of the burst length histograms for tetramethrin-modified channels upon depolarization to −60 mV were 7.69 and 14.46 msec at 22 and 12°C, respectively (Q₁₀= 0.53). Tetramethrin at 10 μm modified 17 and 23% of channels at 22 and 12°C, respectively, indicating that the sensitivity of the sodium channel of rat hippocampal neurons to tetramethrin was almost the same as that of tetrodotoxin-sensitive sodium channels of rat dorsal root ganglion neurons and rat cerebellar Purkinje neurons. The time constants for burst length in tetramethrin-modified sodium channels upon repolarization to −100 mV from −30 mV were 8.26 and 68.80 msec at 22 and 12°C (Q₁₀= 0.12), respectively. The prolongation of tetramethrin-modified whole-cell sodium tail currents upon repolarization at lower temperature was ascribed to a prolongation of opening of each channel. Simple state models were introduced to interpret behaviors of tetramethrin-modified sodium channels. The Q₁₀ values for transition rate constants upon repolarization were extremely large, indicating that temperature had a profound effect on tetramethrin-modified sodium channels. Received: 31 January 2000/Revised: 18 May 2000     

Cardio-electric field during heart ventricle repolarization in hens

Recovery sequence of ventricular epicardium and body surface potential distribution during the ST-T complex in birds, were studied. Recovery sequence of ventricular epicardium in hens appeared to be independent of activation sequence and to be governed by activation-recovery intervals. Inversion of mutual location of positive and negative areas on the body surface in hens corresponded to the end of the QRS complex and the beginning of the ST-T complex.     

Focal warming in the nucleus of the solitary tract prolongs the laryngeal chemoreflex in decerebrate piglets.

The laryngeal chemoreflex (LCR), elicited by a drop of water in the larynx, is exaggerated by mild hyperthermia (body temperature = 40-41 degrees C) in neonatal piglets. We tested the hypothesis that thermal prolongation of the LCR results from heating the nucleus of the solitary tract (NTS), where laryngeal afferents first form synapses in the brain stem. Three- to 13-day-old piglets were decerebrated and vagotomized and studied without anesthesia while paralyzed and ventilated. Phrenic nerve activity and rectal temperature were recorded. A thermode was placed in the medulla, and the brain tissue temperature was recorded with a thermistor approximately 1 mm from the tip of the thermode. When the thermode was inserted into the brain stem, respiratory activity was arrested or greatly distorted in eight animals. However, the thermode was inserted in nine animals without disrupting respiratory activity, and in these animals, warming the medullary thermode (thermistor temperature = 40-41 degrees C) while holding rectal temperature constant reversibly exaggerated the LCR. The caudal raphé was warmed focally by approximately 2 degrees C in four additional animals; this did not alter the duration of the LCR in these animals. Thermodes placed in the NTS did not disrupt respiratory activity, but they did prolong the LCR when warmed. Thermodes that were placed deep to the NTS in the region of the nucleus ambiguus disrupted respiratory activity, which precluded any analysis of the LCR. We conclude that prolongation of the laryngeal chemoreflex by whole body hyperthermia originates from the elevation of brain tissue temperature within in the NTS.     

An infrared thermographic study of surface temperature in relation to external thermal stress in the Mongolian gerbil, Meriones unguiculatus

1. Temperatures of different body surface regions and deep body temperature (Tb) of unrestrained adult Mongolia gerbils exposed to ambient temperatures (Ta) of -10-35 degrees C were measured using infrared (i.r.) thermography and a thermocouple. 2. A strong positive linear relationship between the surface temperature and Ta was found. For Ta range -4-35 degrees C, the slope was lowest for the areas around the eyes and dorsal head, and steepest for the body extremities. At -10 degrees C, surface temperatures of the areas around the eyes and dorsal head were significantly lower then predicted. 3. Tb was lowest at Ta of 25 and 30 degrees C, increased at all temperatures above and up to Ta of -4 degrees C below this range, and began decline at -10 degrees C. 4. The thermoneutral zone (TNZ) is probably between 28 and 32 degrees C, and the absolute lower critical temperature (Tabsl) is probably -4 degrees C. 5. The Mongolian gerbil shows little control of surface temperature and in contrast to larger mammals it has not developed any special thermoregulatory surface areas to regulate heat exchange with its environment. At temperatures below -4 degrees C, this species is unable to maintain the surface temperature of body extremities above the freezing point. 6. It is suggested that the Mongolian gerbil uses mainly behavioral and ecological adaptive strategies to attenuate the stressful effects of its habitat.     

Stabilization of globular proteins via introduction of temperature-activated elastin-based switches

To investigate whether swapping native turns of a globular protein with an elastin-based turn sequence (VPGVG) can increase its thermostability, we have performed molecular dynamics simulations of wild-type chymotrypsin inhibitor 2 (CI2) and variants containing elastin-based turns at 10 degrees C and 40 degrees C. Wild-type CI2 is more stable at 10 degrees C, while both of the variant forms are more stable at 40 degrees C. Detailed analyses indicate that the elastin-based turns do indeed contribute to the inverse temperature behavior of the modified proteins. Therefore, swapping a wild-type turn sequence with an elastin-based turn provides a novel way to both improve stability of target proteins at body temperature and to possibly introduce a temperature-sensitive switch.     

Effect of temperature on the electrical and mechanical activity of lizard ventricular myocardium

Intracellular action potentials and isometric twitches were recorded from lizard ventricles electrically driven at 20 and 4 beats/min and submitted to temperatures changes between 10.5 and 21 degrees C. It was found that cooling induced a depolarization of the diastolic membrane potential ER, which below 15 degrees C exceeded that predictable for a diffusion potential; on the contrary, during the recovery from hypothermia ER underwent a transitory hyperpolarization. Other effects of the low temperature were a decrease of the maximum rate of depolarization, a lengthening of both the action potential duration and the time to peak contraction, an increase of the strength of contraction, in the hearts driven at 20/min it became apparent also an increase of the action potential overshoot. The hypothesis is discussed that the positive inotropic effect of low temperatures may be due not only to a slowing down of the repolarization of the action potential, but also to an increase of the slow inward current intensity.     

Recovery of action potentials and twitches after K-contractures in frog skeletal muscle

To give information about intracellular Ca2+ translocation during and after K-contractures in vertebrate skeletal muscle fibers, we examined recovery of action potentials and twitches after interruption and spontaneous relaxation of K-contractures at low temperature (3 degrees C) that greatly reduced the rate of Ca2+ reuptake by the sarcoplasmic reticulum. On membrane repolarization interrupting K-contractures, the amplitude of both action potentials and twitches recovered quickly, while the falling phase of action potential was markedly slowed at first to prolong its refractory period, so that repetitive stimulation (20 Hz) did not produce a complete tetanus. Meanwhile, on membrane repolarization after spontaneous relaxation of K-contractures, the action potentials were markedly reduced in amplitude and prolonged in duration at first, also resulting in prolonged refractory period. These results are discussed in connection with Ca2+ absorption to the surface and transverse tubule membranes, producing changes in action potential kinetics.     

Effect of high temperature on the direct cortical response]

Acute experiments were conducted on anesthetized cats placed in a thermochamber at a temperature of 45 degrees C. The direct cortical response in suprasylvian convolution of the cortex during hyperthermia and after the restoration of the thermal homeostasis was studied. It was revealed that hyperthermia caused primary inhibition at a temperature of 40 degrees C and above it, and even complete disappearance of the slow negative potential; above 43 degrees C there was found a gradual depression of the dendrite potential. Restoration of body normothermia following high hyperthermia was accompanied by an insignificant tendency to normalization of the slow negative potential parameters. Analysis of the dendrite potential changes on coupled stimuli testified to the fact that high temperature had a preponderant influence on the presynaptic elements of the cortical axodendrite synapses. On the basis of differential action of heat on the component composition of the direct cortical response a conclusion was drawn on the differences in the sensitivity of functionally different cells of the cortex during hyperthermia.     

Immunocytochemical study on the C cells in pig thyroid glands

The distribution of pig thyroid C cells was demonstrated by a immunoperoxidase method using antiserum to porcine calcitonin. The average number of C cells per 4 mm2 counted in the deep and superficial regions was 127 and 55, respectively. The number in the cranial, middle and caudal regions was 60, 128 and 83, respectively. The number of C cells per follicular and C cells (C cell concentration) in deep and superficial regions was 4.9 and 2.6%. It was 3.2, 4.9 and 3.3% in the cranial, middle and caudal regions, respectively. These results indicate that the number and concentration of C cells were not only larger in deep than superficial regions but also in the middle region than in cranial and caudal in pig thyroid gland. These results also indicate that the C cell distribution in pig thyroid gland is the same as that of dog, human, cat, rat, guinea pig, and mouse.