The vicissitudes of the pacemaker current I Kdd of cardiac purkinje fibers

Abstract

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, Ba(2+) was used to block the decay of I (K1). In the presence of Ba(2+) 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 Ba(2+) 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 Ba(2+). In the absence of Ba(2+), I (Kdd) was present in the pacemaker potential range and reversed at E (K). In the presence of Ba(2+), 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.

The ionic bases of the action potential in isolated mouse cardiac Purkinje cell

“…Nevertheless, we cannot rule out contributions from other current mechanisms, including IK dd 23 or calcium waves. 21,24 The molecular correlates of I f in the rabbit have been identified as HCN2 and HCN4 25 .…”

Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node discharge

“…This mechanism could not be the block of I f and might be related to a decrease in potassium conductance. Indeed, in ventricular myocytes [50] and in Purkinje fibers (see [5]), high [K + ] o increases I K1 conductance, although I K1 is far less expressed in SAN dominant pacemaker cells than in ventricular or Purkinje cells. This hypothesis was tested by using barium, that (like cesium) decreases potassium conductance, but (unlike cesium) does not block I f [28].…”

“…In part, this is the result of the disagreement about the SAN dominant pacemaker mechanism [see [4,5]], since adrenergic neuromediators would be expected to change SAN rate by acting on dominant pacemakers.…”

Reduced Ca2+ transport across sarcolemma but enhanced spontaneous activity in cardiomyocytes isolated from left atrium-pulmonary veins tissue of myopathic hamster

“…Our results suggest that LA-PV cardiomyocytes of myopathic hamsters have more frequently automatic discharge, but smaller I Ca,L and I NCX with a shorter APD. The altered electrophysiological properties might favor the occurrence of reentrant rhythms [6,16]. …”