The arrhythmogenic transient inward current iTI and related contraction in isolated guinea‐pig ventricular myocytes.

1. The arrhythmogenic transient inward current, iTI, and contractions were recorded in isolated guinea‐pig ventricular myocytes, after exposure to strophanthidin or low external K+ (0.5 mM), using a single‐microelectrode voltage‐clamp technique and an optical measure of contraction. 2. The inward current, iTI, and after‐contraction occurred on repolarization after a depolarizing pre‐pulse. Longer pre‐pulses to more positive potentials increased the size and reduced the latency of iTI. Oscillatory currents and contractions also occurred during pulses to positive potentials. 3. The voltage dependence of iTI was studied by repolarizing to different potentials after a constant depolarizing pulse. Inward currents preceded after‐contractions at all potentials. The iTI was maximal at about ‐50 mV, diminishing in magnitude at more negative and positive potentials. It remained inward at potentials up to +47 mV. The contraction exhibited a similar voltage dependence. The current‐voltage relation varied in the same cell with longer exposure to glycosides. Thus, the voltage dependence of iTI reflected not only that of an underlying ionic mechanism but also the effects of potential on intracellular Ca2+ oscillations which trigger iTI. 4. Uniformity of internal Ca2+ transients was achieved by clamping to different potentials at the peak of an inward current. The iTI remained inward at positive potentials. An inward tail current, seen on repolarizing during iTI at the end of a depolarizing pre‐pulse, progressively increased at negative potentials. This voltage dependence may be close to that of the Ca2+‐activated inward current responsible for iTI. 5. Replacement of Na+ by Li+ initially increased the magnitude of iTI, but further exposure abolished the inward current, while the after‐contractions continued to increase. The potential dependence of iTI was not affected by exposure to zero Na+. Replacement of Ca2+ by Sr2+ also abolished iTI and the after‐contraction, but the main effect was to slow their occurrence. 6. The voltage dependence of the Ca2+‐activated inward current in guinea‐pig ventricular myocytes leads us to favour electrogenic Na‐Ca exchange current as a major component of iTI, under our experimental conditions.

[1]  A. Mugelli,et al.  An Oscillatory Current in Sheep Cardiac Purkinje Fibers , 1981, Circulation research.

[2]  B. Katzung,et al.  Voltage‐clamp studies of transient inward current and mechanical oscillations induced by ouabain in ferret papillary muscle , 1982, The Journal of physiology.

[3]  J. Deitmer,et al.  Changes in the intracellular sodium activity of sheep heart Purkinje fibres produced by calcium and other divalent cations. , 1978, The Journal of physiology.

[4]  A. Fabiato,et al.  Contractions induced by a calcium‐triggered release of calcium from the sarcoplasmic reticulum of single skinned cardiac cells. , 1975, The Journal of physiology.

[5]  R. Tsien,et al.  Fluctuations in membrane current driven by intracellular calcium in cardiac Purkinje fibers. , 1982, Biophysical journal.

[6]  H. Fozzard,et al.  Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development , 1982, The Journal of general physiology.

[7]  K. MacLeod,et al.  Sodium‐dependent control of intracellular pH in Purkinje fibres of sheep heart. , 1985, The Journal of physiology.

[8]  R. Kass An optical monitor of tension for small cardiac preparations. , 1981, Biophysical journal.

[9]  R. Tsien,et al.  Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. , 1978, The Journal of physiology.

[10]  J. Kimura,et al.  Identification of sodium‐calcium exchange current in single ventricular cells of guinea‐pig. , 1987, The Journal of physiology.

[11]  M. Valdeolmillos,et al.  A study of intracellular calcium oscillations in sheep cardiac Purkinje fibres measured at the single cell level. , 1986, The Journal of physiology.

[12]  R. Tsien,et al.  Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. , 1976, The Journal of physiology.

[13]  D. Noble 6 – Sodium–Calcium Exchange and Its Role in Generating Electric Current , 1986 .

[14]  W. Lederer,et al.  Inotropic and arrhythmogenic effects of potassium‐depleted solutions on mammalian cardiac muscle. , 1979, The Journal of physiology.

[15]  D. Allen,et al.  The effects of low sodium solutions on intracellular calcium concentration and tension in ferret ventricular muscle. , 1983, The Journal of physiology.

[16]  A. Fabiato,et al.  Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles. , 1978, The Journal of physiology.

[17]  W. Lederer,et al.  The arrhythmogenic current ITI in the absence of electrogenic sodium‐calcium exchange in sheep cardiac Purkinje fibres. , 1986, The Journal of physiology.

[18]  M. Vassalle,et al.  On the Mechanism Underlying the Oscillatory Current in Cardiac Purkinje Fibers , 1986, Journal of cardiovascular pharmacology.

[19]  B. Katzung,et al.  Effects of sodium substitutes on transient inward current and tension in guinea‐pig and ferret papillary muscle. , 1985, The Journal of physiology.

[20]  I. Cohen,et al.  Extracellular [K+] fluctuations in voltage-clamped canine cardiac Purkinje fibers. , 1984, Biophysical journal.

[21]  R. Eckert,et al.  Inactivation of Ca channels. , 1984, Progress in biophysics and molecular biology.

[22]  D. Allen,et al.  Oscillations of intracellular Ca2+ in mammalian cardiac muscle , 1983, Nature.

[23]  E. Lakatta,et al.  Frequency modulation and synchronization of spontaneous oscillations in cardiac cells. , 1985, The American journal of physiology.

[24]  R. Tsien,et al.  High selectivity of calcium channels in single dialysed heart cells of the guinea‐pig. , 1984, The Journal of physiology.

[25]  Gary Yellen,et al.  Single Ca2+-activated nonselective cation channels in neuroblastoma , 1982, Nature.

[26]  D. Noble,et al.  The surprising heart: a review of recent progress in cardiac electrophysiology. , 1984, The Journal of physiology.

[27]  松田 博子 Transient depolarization and Spontaneous voltage fluctuations in isolated single cells from guinea pig ventricles : calcium-mediated membrane potential fluctuations , 1984 .

[28]  R. Dehaan,et al.  Caffeine-induced current in embryonic heart cells: time course and voltage dependence. , 1983, The American journal of physiology.

[29]  E. Lakatta,et al.  Calcium‐Dependent Mechanical Oscillations Occur Spontaneously in Unstimulated Mammalian Cardiac Tissues , 1984, Circulation research.

[30]  D. Noble,et al.  Relationship between the transient inward current and slow inward currents in the sino‐atrial node of the rabbit. , 1986, The Journal of physiology.

[31]  E. Neher,et al.  Inward current channels activated by intracellular Ca in cultured cardiac cells , 1981, Nature.

[32]  L. Pott,et al.  Identification of Na-Ca exchange current in single cardiac myocytes , 1986, Nature.

[33]  E. Lakatta,et al.  Cellular calcium fluctuations in mammalian heart: direct evidence from noise analysis of aequorin signals in Purkinje fibers. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[34]  D. Allen,et al.  Characterization of oscillations of intracellular calcium concentration in ferret ventricular muscle. , 1984, The Journal of physiology.

[35]  T. Powell,et al.  A rapid technique for the isolation and purification of adult cardiac muscle cells having respiratory control and a tolerance to calcium. , 1976, Biochemical and biophysical research communications.