Does Ca2+ release from the sarcoplasmic reticulum influence heart rate?

Abstract

1. The present review summarizes the evidence that Ca2+ release from the sarcoplasmic reticulum (SR) is an important contributor to the systolic rise in [Ca2+]i (the Ca2+ transient) and influences the pacemaker firing rate. 2. We believe that the mechanism whereby [Ca2+]i influences firing rate is through the dependence of the Na+-Ca2+ exchanger on [Ca2+]i. 3. Extrusion of Ca2+ by the electrogenic Na+-Ca2+ exchanger produces an inward current that contributes to the pacemaker currents. Confocal images of Ca2+ indicate the distribution of [Ca2+]i and Ca2+ sparks add to the evidence that Ca2+ release from SR is involved in pacemaker activity. 4. The normal pathway for increased heart rate is sympathetic activation; we discuss the evidence that part of the chronotropic effect of beta-adrenoceptor stimulation is through the modulation of SR Ca2+ release. 5. These studies show that Ca2+ handling by the pacemaker cells makes an important contribution to the regulation of pacemaker activity.