Pacemaker current i(f) in adult canine cardiac ventricular myocytes.

1. Single cells enzymatically isolated from canine ventricle and canine Purkinje fibres were studied with the whole‐cell patch clamp technique, and the properties of the pacemaker current i(f) compared. 2. Steady‐state i(f) activation occurred in canine ventricular myocytes at more negative potentials (‐120 to ‐170 mV) than in canine Purkinje cells (‐80 to ‐130 mV). 3. Reversal potentials were obtained in various extracellular Na+ (140, 79 or 37 mM) and K+ concentrations (25, 9 or 5.4 mM) to determine the ionic selectivity of i(f) in the ventricle. The results suggest that this current was carried by both sodium and potassium ions. 4. The plots of the time constants of i(f) activation against voltage were ‘bell shaped’ in both canine ventricular and Purkinje myocytes. The curve for the ventricular myocytes was shifted about 30 mV in the negative direction. In both ventricular and Purkinje myocytes, the fully activated I‐V relationship exhibited outward rectification in 5.4 mM extracellular K+. 5. Calyculin A (0.5 microM) increased i(f) by shifting its activation to more positive potentials in ventricular myocytes. Protein kinase inhibition by H‐7 (200 microM) or H‐8 (100 microM) reversed the positive voltage shift of i(f) activation. This effect of calyculin A also occurred when the permeabilized patch was used for whole‐cell recording. 6. These results indicate i(f) is present in ventricular myocytes. If shifted to more positive potentials i(f) could play a role in ischaemia‐induced ventricular arrhythmias. The negative shift of i(f) in the ventricle might play a role in differentiating non‐pacing regions of the heart from those regions that pace.

[1]  D. Noble,et al.  Adrenaline: Mechanism of Action on the Pacemaker Potential in Cardiac Purkinje Fibers , 1968, Science.

[2]  N. Sperelakis Pacemaker Mechanisms in Myocardial Cells during Development of Embryonic Chick Hearts , 1982 .

[3]  R. Mathias,et al.  Calculation of time constants for intracellular diffusion in whole cell patch clamp configuration. , 1988, Biophysical journal.

[4]  S. Watabe,et al.  Calcium-independent activation of contractile apparatus in smooth muscle by calyculin-A. , 1989, The Journal of pharmacology and experimental therapeutics.

[5]  D DiFrancesco,et al.  A new interpretation of the pace‐maker current in calf Purkinje fibres. , 1981, The Journal of physiology.

[6]  N. Sperelakis,et al.  Identification of the hyperpolarization-activated inward current in young embryonic chick heart myocytes. , 1991, Journal of developmental physiology.

[7]  W. Giles,et al.  Voltage clamp measurements of the hyperpolarization‐activated inward current I(f) in single cells from rabbit sino‐atrial node. , 1991, The Journal of physiology.

[8]  I. Cohen,et al.  Pacemaker current exists in ventricular myocytes. , 1993, Circulation research.

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

[10]  D DiFrancesco,et al.  Pacemaker mechanisms in cardiac tissue. , 1993, Annual review of physiology.

[11]  A. Shrier,et al.  Pacemaker current in single cells and in aggregates of cells dissociated from the embryonic chick heart. , 1992, The Journal of physiology.

[12]  D. DiFrancesco,et al.  Inhibition of the hyperpolarization‐activated current (if) induced by acetylcholine in rabbit sino‐atrial node myocytes. , 1988, The Journal of physiology.

[13]  Dario DiFrancesco,et al.  Direct activation of cardiac pacemaker channels by intracellular cyclic AMP , 1991, Nature.

[14]  A. Noma,et al.  Slow current systems in the A-V node of the rabbit heart , 1980, Nature.

[15]  Y. Earm,et al.  A pace‐maker‐like current in the sheep atrium and its modulation by catecholamines. , 1983, The Journal of physiology.

[16]  R. Mathias,et al.  Limitations of the whole cell patch clamp technique in the control of intracellular concentrations. , 1990, Biophysical journal.

[17]  R. Tsien Mode of Action of Chronotropic Agents in Cardiac Purkinje Fibers , 1974, The Journal of general physiology.

[18]  R. Keynes The ionic channels in excitable membranes. , 1975, Ciba Foundation symposium.

[19]  D. DiFrancesco The cardiac hyperpolarizing-activated current, if. Origins and developments. , 1985, Progress in biophysics and molecular biology.

[20]  N Toda,et al.  The influence of sympathetic stimulation on transmembrane potentials in the S-A node. , 1968, The Journal of pharmacology and experimental therapeutics.

[21]  Zhengfeng Zhou,et al.  Properties of the pacemaker current (If) in latent pacemaker cells isolated from cat right atrium. , 1992, The Journal of physiology.

[22]  D DiFrancesco,et al.  A study of the ionic nature of the pace‐maker current in calf Purkinje fibres. , 1981, The Journal of physiology.

[23]  I. Cohen,et al.  Actions of barium and rubidium on membrane currents in canine Purkinje fibres. , 1983, The Journal of physiology.

[24]  B. Katz,et al.  Production of Membrane Potential Changes in the Frog's Heart by Inhibitory Nerve Impulses , 1955, Nature.

[25]  G. Callewaert,et al.  Single cardiac Purkinje cells: general electrophysiology and voltage‐clamp analysis of the pace‐maker current. , 1984, The Journal of physiology.