title: Frequency-dependence of Vmax in K-depolarized guinea pig ventricle: effects of nifedipine and verapamil.
abstract: 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)
authors.forename: J P
authors.initials: JP
authors.lastname: Woods
authors.forename: T C
authors.initials: TC
authors.lastname: West
mesh_terms: 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*
chemical_list: D014700:Verapamil; D009543:Nifedipine; D011188:Potassium