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

Abstract

The mechanisms responsible for the sino-atrial node resistance to high [K+]o are reviewed with the aim to define the factors that are important in allowing the sino-atrial node (SAN) to continue its spontaneous discharge at [K⁺]_o that suppress the automaticity of Purkinje fibers. It was found that in vivo the inhibition of SAN discharge by high [K⁺]_o becomes progressively more marked as the influence of tonic sympathetic discharge, neural, extraneural and circulating catecholamines is progressively eliminated. However, SAN continues to discharge at a [K⁺]_o of 10.8 mM even after suppression of sympathetic effects, suggesting that intrinsic properties of the SAN are also important. In isolated SAN perfused in vitro, high [K⁺]_o  (10 mM or higher) decreases the maximum diastolic potential and the action potential amplitude of subsidiary pacemakers unmasking a K-insensitive diastolic depolarization (DD). In dominant pacemaker cells, when the threshold potential is missed, an oscillatory afterpotential (V_os) is often superimposed on early DD which contributes to maintain the rate nearly normal. During late DD, gradually increasing oscillatory prepotentials (ThV_os) may initiate an action potential and allow the SAN to discharge at slow rate. In quiescent SAN, on decreasing high [K⁺]_o, the resumption of spontaneous activity is caused by ThV_os. In high [K⁺]_o, Cs⁺ and Ba²⁺ may induce spontaneous activity in quiescent SAN and accelerate spontaneously active SAN. A low [Ni²⁺]_o does not suppress SAN whereas nifedipine does; and high [Ca²⁺]_o induces spontaneous discharge in quiescent SAN. Tetrodotoxin and low [Na⁺]_o often cause conduction block. In conclusion, the resistance of SAN to high [K⁺]_o is due to several factors: 1) presence of heavy sympathetic innervation; 2) small or absent I_K1 in dominant pacemaker cells; 3) depolarization of SAN subsidiary pacemakers which eliminates a DD sensitive to high [K⁺]_o and diminishes the electrotonic drag on dominant pacemaker cells; 4) presence of a K⁺- and Cs⁺-insensitive DD at less negative levels which is apparently due to the decay of I_K; 5) presence of a V_os that facilitates the attainment of the threshold by DD; 6) action of ThV_os which can maintain a slower rhythm or initiate one again; and 7) effects of Ca²⁺ on the oscillatory phenomena and of Na⁺ on excitation.

Key Words

Molecular biology - mechanisms of arrhythmogenesis 
sino-atrial node, Purkinje fibers, high K+ , sympathetic system, experimental arrhytmology, OA