Role of action potential configuration and the contribution of Ca(2+) and K(+) currents to isoprenaline-induced changes in canine ventricular cells

BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca(2+) current (I(Ca) ), slow delayed rectifier K(+) current (I(Ks) ) and fast delayed rectifier K(+) current (I(Kr) ) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials.     

Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells

Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3–30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I_Ca, I_to, I_K1, I_Kr, and I_Ks. Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.     

绞股蓝总皂甙对单个豚鼠心室肌细胞的钙、钠、钾电流及动作电位的影响

目的研究绞股蓝总皂甙（ＧＰ）对成年豚鼠单个心室肌细胞的动作电位（ＡＰ）、Ｌ－型钙通道电流（ＩＣａ）、快钠通道电流（ＩＮａ）以及内向整流钾通道电流（ＩＫ１）的影响。方法膜片钳全细胞记录。结果５０ｍｇＬ－１ＧＰ能使动作电位时程（ＡＰＤ９０）由给药前的（７０８±２４）ｍｓ缩短到给药后的（３９６±１６）ｍｓ（Ｐ＜０．０１），抑制率５８．１％，动作电位幅值（ＡＰＡ）由给药前的（１２１±７．２）ｍＶ降到给药后的（８６±８．６）ｍＶ（Ｐ＜０．０１），抑制率２４．１％，静息膜电位无明显影响；５～５０ｍｇＬ－１的ＧＰ能浓度依赖性阻滞ＩＣａ和ＩＮａ，但对ＩＫ１无明显影响。结论ＧＰ对缺血心肌的保护作用在于减少“钙超载”和抑制异常兴奋性的产生。     

Effects of cibenzoline,a new class Ia antiarrhythmic drug,on various membrane ionic currents and action potentials of guinea-pig ventricular cells

We examined the effects of cibenzoline, a new class Ia antiarrhythmic drug, on various membrane ionic currents and action potentials of guinea-pig single ventricular cells, using patch clamp techniques in whole-cell configuration. Action potentials and the membrane currents were evoked at a clamping rate of 0.2 Hz, and all experiments were performed at 32–33°C.

Effects of goniopora toxin on the action potential and membrane currents of guinea-pig single ventricular cells

Summary The effects of Goniopora toxin (GPT), a polypeptide isolated from a coral, Goniopora spp., on action potential and membrane currents were studied in single ventricular cells of the guinea-pig using the whole-cell clamp technique with a single patch electrode. GPT at a concentration of 10 nmol/l prolonged the duration of the action potential without significant change in the resting membrane potential and action potential amplitudes. This prolongation became more evident at lower stimulus frequencies and persisted after washing with toxin-free solution. Tetrodotoxin (TTX, 1 mol/l), but not Co²⁺ (2 mmol/1), abolished the prolonged action potential. Under voltage-clamp conditions, a sustained inward current, not present in the control, followed the transient inward current during depolarizing pulses in the GPT-treated cells. The current-voltage relationship for the sustained inward current was much the same as that for the fast sodium current reported in rat single ventricular cells (Brown et al. 1981). Both the sustained and transient currents were abolished by the shift of holding potential in the direction of depolarization and reappeared after repolarization; the reappearance of the sustained current was much slower than that of the transient current. TTX but not Co²⁺ abolished both the sustained and transient inward currents. Calcium current and time-independent current were not affected by GPT. Time-dependent outward current induced by large depolarizing pulses was attenuated by GPT. From these results, it is suggested that GPT predominantly acts on the sodium channels in cardiac muscle, to give rise to a sustained sodium current which is responsible for the prolongation of action potential, and that the sodium channels modified by this toxin may reveal slow inactivation and slow recovery from inactivation as compared with those of unmodified sodium channels. Send offprint requests to I. Muramatsu     

Effects of 17β-estradiol on action potentials and ionic currents in male rat ventricular myocytes

This study describes electrophysiological effects of estrogens in isolated male rat ventricular myocytes. According to the literature these cells do not express the nuclear estrogen receptor. Action potentials or membrane currents were recorded in the whole-cell configuration with standard techniques. Action potential durations (APD) measured at a level of 0 mV (APD 0) and –70 mV (APD –70) were prolonged by 17β-estradiol (0.5 Hz stimulation frequency, 24–26° C). Threshold concentration was 1 μmol/l. At the highest concentration used (30 μmol/l) no saturation of the response was reached and APD 0 was 162% and APD –70 was 230% of the respective control. The resting potential remained unaffected in most cells. The prolongation induced by 17β-estradiol developed rapidly and reached a steady state 10 min after start of hormone superfusion. Effects of estrogen were completely reversible during 10–15 min wash-out with hormone-free solution. The extent of prolongation (10 μmol/l 17β-estradiol) was frequency dependent. Expressed as percentage of the respective control APD 0 (or APD –70) was 115% (188%) at 0.05 Hz, 118% (163%) at 0.5 Hz and 99% (129%) at 5 Hz stimulation frequency. The response was stereoselective, because 30 μmol/l 17α-estradiol did not prolong action potentials (APD 0: 101%, APD –70: 104% of the respective control, 0.5 Hz stimulation frequency). The endogenous estrogens estrone and estriol were less effective than 17β-estradiol. With 30 μmol/l estrone (0.5 Hz stimulation frequency) APD 0 was 103% and ADP-70 148% of control and with 30 μmol/l estriol APD 0 was 135% and APD –70 137% of control. The prolongation of action potentials can be explained by inhibition of transient outward current which, in rat ventricle, is composed of fast (i _to,f) and slowly (i _to,s) inactivating components. At 30 μmol/l 17β-estradiol i _to,f was reduced to 50% and i _to,s to 43% of their maximal amplitudes. The voltage sensor of i _to,f or i _to,s was hardly affected. Additionally, 17β-estradiol decreased the calcium current (i _Ca,L) to 76% (10 μmol/l) and 38% at 30 μmol/l. The inwardly rectifying potassium current (i _K1) was reduced partly with 30 μmol/l 17β-estradiol and its amplitude was 72% of control at –90 mV (inward current flow) and 65% at –40 mV (outward current flow). These results show that 17β-estradiol is active in cardiac cells which do not express the nuclear estrogen receptor. The hormone exerts class III activity and reduces calcium inward current. These effects, however, occur in vitro with concentrations above the physiological level and therefore may be without significance in vivo. Received: 6 May 1997 / Accepted: 18 October 1997     

Effects of metoprolol on action potential and membrane currents in guinea-pig ventricular myocytes

Summary The effects of the beta-adrenoceptor antagonist metoprolol on action potentials and membrane currents were studied in single guinea-pig ventricular myocytes. The experiments were carried out using the nystatin-method of whole-cell technique. This method was used in order to prevent the run-down of the calcium current. Metoprolol at concentrations of 10–100 mol/l shortened action potential in a dose-dependent way. The drug only decreased resting membrane potential at a concentration of 100 mol/1 in two out of five cells. Under voltage-clamp conditions, metoprolol blocked the high threshold calcium current at concentrations of 30 and 100 mol/l to 82 ± 4% and 73 ± 5% from control, respectively. The drug decreased the inward rectifying potassium current in a concentration-dependent manner. This effect was evident for inward current at voltages negative to the apparent reversal potential and for outward current at voltages between –30 and –80 mV. This blocking effect on the inward rectifying potassium current can explain the effect on resting membrane potential. At voltages positive to –30 mV metoprolol increased a time-independent outward current. This metoprolol-enhanced outward current was blocked by barium and cesium. This result suggests that the metoprolol-enhanced current is carried by potassium. The current component enhanced by metoprolol was not sensitive to glibenclamide and tetraethylammonium applied externally, which suggests that the adenosine triphosphate-sensitive channel is not the target of metoprolol. The activation of this time-independent outward current by metoprolol and the blocking effects on the calcium current seem to explain the shortening in action potential induced by the drug. Send offprint requests to J. Sánchez-Chapula at the above address     

Efects of benzyltetrahydropalmatine ?

ＥｆｅｃｔｓｏｆｂｅｎｚｙｌｔｅｔｒａｈｙｄｒｏｐａｌｍａｔｉｎｅｏｎａｃｔｉｏｎｐｏｔｅｎｔｉａｌｓａｎｄｄｅｌａｙｅｄｒｅｃｔｉｆｙｉｎｇｐｏｔａｓｉｕｍｃｕｒｅｎｔｓｉｎｇｕｉｎｅａｐｉｇｖｅｎｔｒｉｃｕｌａｒｍｙｏｃｙｔｅｓＤＡＩＳｈｕｉ－Ｐ...     

Effects of norfluoxetine on the action potential and transmembrane ion currents in canine ventricular cardiomyocytes

Norfluoxetine is the most important active metabolite of the widely used antidepressant compound fluoxetine. Although the cellular electrophysiological actions of fluoxetine are well characterized in cardiac cells, little is known about the effects of its metabolite. In this study, therefore, the effects of norfluoxetine on action potential (AP) configuration and transmembrane ion currents were studied in isolated canine cardiomyocytes using the whole cell configuration of patch clamp techniques. Micromolar concentrations of norfluoxetine (1–10 M) modified AP configuration: amplitude and duration of the AP and maximum velocity of depolarization were decreased in addition to depression of the plateau and elimination of the incisura of AP. Voltage clamp experiments revealed a concentration-dependent suppression of both L-type Ca²⁺ current, I_Ca (EC₅₀=1.13±0.08 M) and transient outward K⁺ current, I_to (EC₅₀=1.19±0.17 M) having Hill coefficients close to unity. The midpoint potential of the steady-state inactivation of I_Ca was shifted from –20.9±0.75 mV to –27.7±1.35 mV by 3 M norfluoxetine (P<0.05, n=7). No such shift in the steady-state inactivation curve was observed in the case of I_to. Similarly, norfluoxetine caused no change in the steady-state current–voltage relationship of the membrane or in the density of the inward rectifier K⁺ current, I_K1. All these effects of norfluoxetine developed rapidly and were fully reversible. Comparing present results with those obtained previously with fluoxetine, it can be concluded that norfluoxetine displays stronger suppression of cardiac ion channels than fluoxetine. Consequently, the majority of the cardiac side effects observed during fluoxetine treatment are likely to be attributed to its metabolite norfluoxetine.     

蛇床子素对心肌慢反应动作电位及右心房自搏频率的影响

用细胞内微电极技术，观察了蛇床子素（Ｏｓｔ）对离体豚鼠乳头状肌ＢａＣｌ２高ＫＣｌ除极化及家兔窦房结慢反应动作电位的影响。结果表明。Ｏｓｔ抑制Ｂａ２＋诱发的自发电活动：降低高Ｋ＋除极化慢反应动作电位的幅度（ＡＰＡ）及动作电垃最大上升速率（Ｖｍａｘ），并缩短５０％动作电垃时程（ＡＰＤ５０），延长９０％动作电位时程（ＡＰＤ９０）；对家兔离体窦房结优势起搏细胞窦搏周期（ＳＣＬ），ＡＰＡ及Ｖｍａｘ亦有抑制作用。此外，对离体豚鼠右房负性频率作用。似与激动Ｍ胆碱能受体或阻滞β肾上腺圭能受体无关，与钙拮抗剂维拉帕米相似．结果提示。Ｏｓｔ具有钙拮抗作用．     

Effects of ropinirole on action potential characteristics and the underlying ion currents in canine ventricular myocytes

In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the dopamine receptor agonist ropinirole. In the present study, therefore, the concentration-dependent effects of ropinirole on action potential morphology and the underlying ion currents were studied in enzymatically dispersed canine ventricular cardiomyocytes using standard microelectrode, conventional whole-cell patch clamp, and action potential voltage clamp techniques. At concentrations?≥?1 μM, ropinirole increased action potential duration (APD₉₀) and suppressed the rapid delayed rectifier K⁺ current (I _Kr) with an IC₅₀ value of 2.7?±?0.25 μM and Hill coefficient of 0.92?±?0.09. The block increased with increasing depolarizations to more positive voltages, but paradoxically, the activation of I _Kr was accelerated by 3 μM ropinirole (time constant decreased from 34?±?4 to 14?±?1 ms). No significant changes in the fast and slow deactivation time constants were observed with ropinirole. At higher concentrations, ropinirole decreased the amplitude of early repolarization (at concentrations?≥?10 μM), reduced the maximum rate of depolarization and caused depression of the plateau (at concentrations?≥?30 μM), and shortened APD measured at 50% repolarization (at 300 μM) indicating a concentration-dependent inhibition of I _to, I _Na, and I _Ca. Suppression of I _Kr, I _to, and I _Ca has been confirmed under conventional patch clamp and action potential voltage clamp conditions. I _Ks and I _K1 were not influenced significantly by ropinirole at concentrations less than 300 μM. All these effects of ropinirole were fully reversible upon washout. The results indicate that ropinirole treatment may carry proarrhythmic risk for patients with inherited or acquired long QT syndrome due to inhibition of I _Kr—especially in cases of accidental overdose or intoxication.     

Analysis of arrhythmogenic profile in a canine model of chronic atrioventricular block by comparing in vitro effects of the class III antiarrhythmic drug nifekalant on the ventricular action potential indices between normal heart and atrioventricular block heart

The chronic atrioventricular block dog is a useful model for predicting the future onset of drug-induced long QT syndrome in clinical practice. To better understand the arrhythmogenic profile of this model, we recorded the action potentials of the isolated ventricular tissues in the presence and absence of the class III antiarrhythmic drug nifekalant. The action potential durations of the Purkinje fiber and free wall of the right ventricle were longer in the chronic atrioventricular block dogs than in the dogs with normal sinus rhythm. Nifekalant in concentrations of 1 and 10 microM prolonged the action potential durations of Purkinje fiber and the free wall in a concentration-dependent manner. The extent of prolongation was greater in the chronic atrioventricular block dogs than in the normal dogs. However, increase of temporal dispersion of ventricular repolarization including early afterdepolarization was not detected by nifekalant in either group of dogs, indicating lack of potential to trigger arrhythmias in vitro. These results suggest that the ventricular repolarization delay in the chronic atrioventricular block model by nifekalant may largely depend on the decreased myocardial repolarization reserve, whereas the trigger for lethal arrhythmia was not generated in the in vitro condition in contrast to the in vivo experiment.     

藻酸双酯钠对豚鼠心室肌细胞动作电位及L-型钙电流的影响

目的　研究藻酸双酯钠 (PSS)对豚鼠心室肌细胞动作电位和L 型钙电流的影响。方法　采用全细胞膜片钳记录技术。结果　PSS明显缩短动作电位时程 (APD) ,5 0、10 0和 2 0 0mg·L-1浓度 ,分别使APD90 缩短 2 4 9% (P <0 0 5 ,n=6 )、37 7%和 4 7 7% (P <0 0 1,n =6 ) ,使APD50 缩短2 1 1% (P <0 0 5 ,n =6 )、4 5 0 %和 6 3 2 % (P <0 0 1,n =6 ) ,呈明显的剂量依赖关系。PSS浓度依赖性减小L 型钙电流 (Ica L) ,5 0、10 0和 2 0 0mg·L-1浓度 ,分别使其峰值降低34 3% (P <0 0 5 ,n =6 )、5 8 4 %和 74 9% (P <0 0 1,n =6 )。随着PSS浓度的增加 ,L 型钙电流的I U曲线逐渐上移 ,但其最大激活电压保持为 0mV不变。结论　PSS明显缩短APD ,抑制Ica L,且呈浓度依赖关系     

豚鼠心室肌细胞延迟整流钾电流快慢成分在生长发育过程中的变化

目的研究豚鼠从幼年到成年的发育过程中心室肌细胞延迟整流钾电流快(IKr)、慢成份(IKs)及动作电位的变化。方法酶解法急性分离新生、幼年及成年3个不同年龄阶段豚鼠心室肌细胞。(1)室温下采用全细胞膜片钳技术首先记录总的延迟整流钾电流IK,再加入选择性IKr阻断剂E-4031区分IKr和IKs,计算各成份尾电流密度;(2)采用打孔膜片钳技术观察动作电位在生长发育过程中的变化。结果(1)从新生、幼年到成年3个阶段的发育过程中,豚鼠心室细胞IKr和IKs的电流密度呈增长趋势,但二者的变化方式不同。IKs呈逐渐递增式发育,表现为幼年组在-30～+50 mV范围内均明显高于新生组,成年组亦明显高于幼年组;而幼年组IKr的电流密度在-10～+50 mV范围内高于新生组,但幼年与成年组无明显差别。(2)在1Hz的刺激频率下,豚鼠心室肌细胞90%复极的动作电位时程APD90随动物年龄的增长明显延长。结论 (1)豚鼠从出生、幼年到成年发育过程中心室肌细胞IKr和IKs电流密度呈不同方式增长;(2)豚鼠心室肌细胞动作电位时程出生至成年逐渐延长,提示内向电流成分在发育过程中发挥重要作用。     

槲寄生黄酮甙对心脏快反应动作电位的效应

用玻璃微电极术观察VCF对狗心脏浦氏细胞和豚鼠心室乳头状肌细胞快反应动作电位(FAP)的影响;并利用选择性膜通道阻滞剂初步分析VCF对FAP各相跨膜离子流的影响。100 μg·ml~(-1) VCF加速FAP复极进程,使 △ERP/△API)比值增加,该作用与减少I_(si)及增加I_x有关。提示VCF抗快速心律失常机制主要与其相对延长ERP消除折返有关。     

Electrophysiologic effects of nicorandil,a new antianginal agent,on action potentials and membrane currents of rabbit atrioventricular node

Summary Electrophysiologic effects of nicorandil, a newly developed coronary vasodilator, on the atrioventricular (AV) node were studied using space-clamped small preparations of the rabbit AV node. At the concentrations of 10^–6, 10^–5 and 10^–4 mol/l, this drug did not cause significant changes in the action potential characteristics including the spontaneous firing frequency, overshoot, maximum diastolic potential, maximum rate of depolarization and action potential duration. When the resting membrane potential of the AV node was obtained by a superfusion with verapamil and then nicorandil was added to the perfusate, no hyperpolarization was observed. This was in sharp contrast to the reported hyperpolarizing action of this drug on the atrial muscle, Purkinje fibres and vascular smooth muscle where the resting potential is much more negative. On the other hand, voltage clamp experiments using double microelectrode techniques revealed that 10^–5 to 10^–4 mol/l nicorandil increased the steady-state outward current at potentials positive to –40 mV and the steady-state inward current at potentials negative to –40 mV. Such a nicorandil-sensitive component of the steady-state current had an average reversal potential of –41.8 mV (n = 5). This component was considered to reflect changes in the time-independent background current, although, at more negative potential levels, it may partially reflect an increase in the hyperpolarization activated inward current (i _h). Nicorandil, at the concentrations of 10^–5 and 10^–4 mol/l, increased the slow inward current (i _si) by 10.8% (n = 5, p < 0.01). As the inactivation kinetics of the i _si was not affected after the application of nicorandil, the increase in the may well be attributed to an increase in the fully activated i _si (i _si). It was also shown that the increase in the i _si was not mediated by neurotransmitters, as an increase of a similar degree was again observed in the presence of either propranolol or atropine. The apparent discrepancy between the effects of nicorandil on the action potential configuration and on the membrane currents may have resulted from cancellations between the inward increase in the i _si and the outward increase in the background current during the action potential. Possible implications of these nicorandil effects in modifying AV conduction were discussed. Send offprint requests to Y. Watanabe at the above address     

普罗帕酮及其对映体对豚鼠心室乳头肌动作电位的影响

用细胞内微电极法研究普罗帕酮消旋体及两对映体对豚鼠右心室乳头肌快反应动作电位（FAP）和慢反应动作电位（SAP）的作用. 普罗帕酮消旋体及两对映体均浓度依赖性地降低FAP和SAP的0相最大除极速率（V_max）和动作电位幅值（APA）, 3药≤3 μmol·L^-1时均延长动作电位时程（APD）. 10 μmol·L^-1时, APD₅₀ 和APD₉₀反缩短至给药前水平,(R)-普罗帕酮延长FAP的APD₂₀而(S)-普罗帕酮则无影响,两组间有显著性差异（P<0.05）. 3药对FAP和SAP静息电位, V_max, APA, APD₅₀及APD₉₀影响均无显著性差异. 结果表明, 普罗帕酮两对映体的钠通道阻滞作用及钙拮抗作用无差异,对心肌动作电位平台期内向钠和/或钙离子流的作用可能表现立体选择性.     

Effects of propranolol on premature action potentials in canine Purkinje and ventricular muscle.

We compared the effects of a low (0.09 microgram/ml) concentration of propranolol expected to produce only beta-adrenoceptor blockade and a high concentration (0.9 microgram/ml) expected to produce additional direct local anesthetic-like electrophysiological effects on basic and premature action potentials. Both isolated dog cardiac Purkinje and ventricular muscle fibers were examined using conventional microelectrode techniques. The low concentration of propranolol produced no significant electrophysiological change in either fiber type. The high concentration of propranolol shortened the action potential duration and refractoriness while decreasing the maximal upstroke velocity (Vmax) in both Purkinje and ventricular muscle fibers at a constant basic cycle length. In Purkinje fibers, the high concentration also slowed the kinetics of restitution of the action potential duration (tau c from 124.6 +/- 6.5 to 201.4 +/- 16.0 ms, p less than 0.01, n = 7), slowed the recovery kinetics of Vmax, and shifted the early portion of the normalized restitution curve toward longer action potential duration values in both fiber types. The range of premature action potential durations, defined as the difference between action potential durations during the first 100 ms of restitution, was decreased by the high concentration of propranolol in both Purkinje and ventricular muscle fibers by 39.5% and 33.9%, respectively. These findings indicate that (a) low concentrations of propranolol produced no direct electrophysiological effect, and (b) high concentrations of propranolol produced several potential antiarrhythmic effects in addition to the previously reported effects on Vmax and the action potential duration.     

Oscillatory transient inward currents in ventricular myocytes of healthy versus myopathic Syrian hamster

The present experiments were performed in order to study abnormal action potential configuration and ion channel activity in ventricular myocytes obtained from 23 male myopathic Syrian hamsters (Biobreeders strain 14.6, 32-52 weeks old) compared with 10 age-matched healthy control hamsters (Biobreeders F1B) by means of whole-cell patch-clamp techniques. The results show that the myopathic myocytes had a longer action potential duration, a reduced transient outward K(+) current on depolarization and a smaller transient inward current on repolarization after prolonged depolarizing pulses (> 500 msec). However, the L-type Ca(2+) current and the inwardly rectifing K(+) current were not significantly different from those of healthy myocytes. The oscillatory transient inward currents could be diminished by treatment with ryanodine (0.01-1 micromol/L), a sarcoplasmic reticulum (SR) Ca(2+) release channel blocker, or with Na(+)-free superfusate. We conclude that the hereditary myopathic hamsters are less likely to develop delayed after depolarization-related transient inward currents and triggered arrhythmias owing to a smaller SR Ca(2+) content.