We tested the assumption that nifedipine blocks L-type calcium current 
[I(Ca(L))] at +10 mV and unmasks Na(+)/Ca(2+) exchange-triggered contractions in 
guinea pig isolated ventricular myocytes. Voltage-clamp pulses elicited I(Ca(L)) 
at +10 mV and evoked contractions in myocytes superfused with Tyrode's solution 
(35 degrees C). Nifedipine blocked I(Ca(L)) with an IC(50) of 0.3 microM; this 
decreased to 50 nM at a holding potential of -40 mV, indicating preferential 
block of inactivated L-type Ca(2+) channels. Use-independent block of I(Ca(L)) 
increased with concentration (10-100 microM) and application time when 
nifedipine was rapidly applied (t(1/2) = approximately 0.2 s) during rest 
intervals (5-30 s). The fraction of use-dependent block of I(Ca(L)) diminished 
with increasing drug concentration. Nifedipine also accelerated I(Ca(L)) 
inactivation on the first test pulse. The combination of 30 microM nifedipine/30 
microM Cd(2+) (Nif 30/Cd 30) was as effective as 100 microM nifedipine to 
suppress I(Ca(L)) on the first test pulse at +10 mV. The incidence of complete 
block of contractions, as for complete block of I(Ca(L)), increased as a 
function of nifedipine concentration and application time. Neither nifedipine 
nor Nif 30/Cd 30 affected Na(+)/Ca(2+) exchange current at +10 to +100 mV. 
Contractions at +100 mV, although as large as those at +10 mV, were delayed in 
onset and resistant to nifedipine or Nif 30/Cd 30. We conclude that 
nifedipine-sensitive I(Ca(L)) triggers contractions at +10 mV, whereas 
nifedipine-resistant Na(+)/Ca(2+) exchange current initiates those at +100 mV.