Frequency-dependence of Vmax in K-depolarized guinea pig ventricle: effects of nifedipine and verapamil.
Right ventricular strips from guinea pig hearts were used to compare the effects of nifedipine and verapamil on the maximal upstroke velocity (Vmax) of rapid depolarization in potassium-depolarized preparations. The Vmax was used as an indirect measure of the slow inward current (Isi). Barium (0.8 mM) was added to the Tyrode solution to restore excitability of the K-depolarized tissue. The effects of nifedipine and verapamil on rested state Vmax (VmaxRS), frequency-dependent changes in Vmax, and recovery of Vmax as a function of diastolic interval were studied. The depression of Vmax at rested state (RS), following 3-5-min rest, was concentration-dependent for both drugs, although the effect of nifedipine was greater. The percentage depression of VmaxRS by nifedipine was 24.3 +/- 6.4 at 10(-8)M, 51.3 +/- 2.6 at 5 X 10(-8)M, and 74.0 +/- 1.0 at 10(-7)M. For verapamil the values were 6.2 +/- 3.8 at 10(-7)M, 13.1 +/- 0.9 at 5 X 10(-7)M, and 42.0 +/- 0.5 at 10(-6)M. The depression of Vmax by each drug was frequency-dependent over a range from 0.05 to 2.0 Hz. Frequency-dependence was quantitatively greater with verapamil. The kinetics of recovery of Vmax were assessed by means of paired stimuli given at varying diastolic intervals during recovery from a RS depolarization. The recovery curve was biexponential. In the drug-free condition, the time constant for the first phase of recovery (Tr1) was 140 +/- 12 ms and the time constant for the second phase (Tr2) was 2689 +/- 146 ms.(ABSTRACT TRUNCATED AT 250 WORDS)
Woods
J P
JP
West
T C
TC
D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil; D009543:Nifedipine; D011188:Potassium