Calcium‐dependent modulation of the plateau phase of action potential in isolated ventricular cells of rabbit heart

[Ca2+]i-dependent modulation of the action potential has been studied in Fura-2 dialysed ventricular myocytes of the rabbit using the whole-cell current-clamp method. Fifteen consecutive action potentials (AP1-AP15) and [Ca2+]i transients were elicited at a frequency of 0.2 Hz. A single, brief application of caffeine (during AP9) first enhanced and thereafter attenuated the [Ca2+]i transients accompanying AP9 and AP10-AP12, respectively. This approach provided direct comparison between time courses of action potentials: during the initial steady state (e.g. AP8) and when Ca2+ release from the sarcoplasmic reticulum was increased by caffeine (AP9) or decreased by depletion (AP10). The increase in [Ca2+]i facilitated repolarization and decreased action potential duration. However, action potentials at reduced Ca2+ release (AP10) had longer duration than during steady state. The caffeine-induced changes in L-type Ca2+ current (ICa,L), during voltage-clamp conditions partially explained the effects of caffeine on action potentials. When ICa,L was blocked by 500 micromol L-1 Cd2+, enhanced [Ca2+]i transients revealed an extra current component which was outward at +10 mV and inward at the resting membrane potential (most probably the transient inward current). In the presence of Cd2+, however, AP8 and AP10 had identical time courses, suggesting that ICa,L alone was responsible for the lengthening of AP10. Alterations in the transmembrane Na+ gradient resulted in changes of the steady state action potential durations (AP8) consistently with the expected modulation of the Na+-Ca2+ exchange current. However, the contribution of this current to the [Ca2+]i-dependent behaviour of action potential plateau could not be demonstrated.