13th International Congress
THE "NEW FRONTIERS"
OF ARRHYTHMIAS 1998

January 24-31, 1998
Marilleva, Trento, Italy

RT-84

Mechanisms underlying the sino-atrial node resistance to high [K⁺]_o

Mario Vassalle.
Department of Physiology, State University of New York, New York, USA

Introduction

Spontaneously active Purkinje fibers perfused in vitro become quiescent when the [K⁺] of Tyrode solution is increased from 2.7 to 5.4 mM¹. In fact, the fibers are usually quiescent even at 4.0 mM [K⁺]_o². In contrast, the sino-atrial node continues to discharge spontaneously even when [K⁺]_o is increased in excess of 10-15 mM, both in vitro^3-6 and in vivo^7,8. In vivo, the sino-atrial node continues to discharge at concentrations at which the atrial fibers become inexcitable and quiescent^7,8.

The different behavior of SAN and of Purkinje fibers to high [K⁺]_o could be due to several reasons. One obvious possibility is the much higher density of sympathetic innervation of SAN compared to that of Purkinje fibers⁹. Catecholamines antagonize the depressant effect of high [K⁺]_o on cardiac excitability and conduction¹⁰. Therefore, they could also be more effective in counteracting the effects of high [K⁺]_o   in SAN than in Purkinje fibers in virtue of the SAN more abundant sympathetic innervation.

Another possible reason is that the membrane characteristics of the SAN cells are different from those of Purkinje fibers and these different characteristics may play an important role in the SAN resistance to high [K⁺]_o. In fact, this question bears on the present disagreement about the ionic nature of the pacemaker currents in SAN and in Purkinje fibers. Thus, it has been proposed that the pacemaker current is the hyperpolarization-activated inward current If in both SAN and Purkinje fibers^11,12; or that, instead, the pacemaker current is the decaying delayed rectifier current IK in SAN^12-15 and If in Purkinje fibers^16-19.

If the pacemaker current were to be the same If in both SAN and Purkinje fibers, it would be necessary to consider what possibly could cause the many differences (including the different sensitivity to high [K⁺]_o) between SAN and Purkinje fiber automaticity. Instead, if the pacemaker current were IK in SAN, the resistance to high  [K⁺]_o of SAN could be accounted for by the resistance^20,21 of IK to high [K⁺]_o. Still, in SAN high [K⁺]_o increases I_f^22,23 and this could be important in maintaining the spontaneous discharge in high [K⁺]_o. However, also in Purkinje fibers high [K⁺]_o  increases I_f^17,18, and therefore (if I_f were the pacemaker current) the suppression of spontaneous discharge by high [K⁺]_o   in Purkinje fibers would require additional factors.

Another possibility is that the pacemaker current in Purkinje fibers is not If, but the decaying potassium current IKdd (formerly I_K2)^24-26. Since high [K⁺]_o blocks I_Kdd²⁶, that could account for the decrease of diastolic depolarization amplitude and suppression of spontaneous discharge in Purkinje fibers exposed to relatively small increments in [K⁺]_o.

My aim is to present evidence indicating that the different sensitivity of SAN and Purkinje fibers to high [K⁺]_o is mainly due to differences in pacemaker mechanisms and that the resistance of SAN to high [K⁺]_o is consistent with decay of I_K as the predominant mechanism of SAN pacemaking.