The vicissitudes of the pacemaker current I (Kdd) of cardiac purkinje fibers.

The mechanisms underlying the pacemaker current in cardiac tissues is not agreed upon. The pacemaker potential in Purkinje fibers has been attributed to the decay of the potassium current I Kdd. An alternative proposal is that the hyperpolarization-activated current I f underlies the pacemaker potential in all cardiac pacemakers. The aim of this review is to retrace the experimental development related to the pacemaker mechanism in Purkinje fibers with reference to findings about the pacemaker mechanism in the SAN as warranted. Experimental data and their interpretation are critically reviewed. Major findings were attributed to K+ depletion in narrow extracellular spaces which would result in a time dependent decay of the inward rectifier current I K1. In turn, this decay would be responsible for a “fake” reversal of the pacemaker current. In order to avoid such a postulated depletion, Ba2+ was used to block the decay of I K1. In the presence of Ba2+ the time-dependent current no longer reversed and instead increased with time and more so at potentials as negative as −120 mV. In this regard, the distinct possibility needs to be considered that Ba2+ had blocked I Kdd (and not only I K1). That indeed this was the case was demonstrated by studying single Purkinje cells in the absence and in the presence of Ba2+. In the absence of Ba2+, I Kdd was present in the pacemaker potential range and reversed at E K. In the presence of Ba2+, I Kdd was blocked and I f appeared at potentials negative to the pacemaker range. The pacemaker potential behaves in a manner consistent with the underlying I Kdd but not with I f. The fact that I f is activated on hyperpolarization at potential negative to the pacemaker range makes it suitable as a safety factor to prevent the inhibitory action of more negative potentials on pacemaker discharge. It is concluded that the large body of evidence reviewed proves the pacemaker role of I Kdd (but not of I f) in Purkinje fibers.