Figure 3.

DHP effects on heart and smooth muscle. (A) Representative experiment illustrating drug effects on cardiac ventricle contractility in Langendorff hearts from WT or homozygous mutant Ca_v1.2DHP–/– mice. Electrically stimulated hearts were superfused with isradipine (ISR) at concentrations of 0.5 ∝M, 1 ∝M, 2.5 ∝M, and 10 ∝M or with 1 ∝M verapamil (VER) (see Results). (B) Percent inhibition of contractility in six WT (black bars) and seven mutant (white bar) mice. Statistical significance: P < 0.001 (compared with Mut; one-way ANOVA followed by the Bonferroni multiple-comparison test); *P < 0.05 (compared with contractility in the absence of isradipine, 100%; one-sample Student t test). Data from 1 ∝M and 2.5 ∝M isradipine (mean ± range of n = 2) were not included in the significance analysis. (C) BayK-induced (1 ∝M) contraction of aortic smooth muscle rings from WT (n = 10) or mutant mice (n = 10). P < 0.001 (Ca_v1.2DHP–/– vs. WT; unpaired Student's t test). (D) Effect of isradipine (1 ∝M) on aortic smooth muscle rings isolated from WT (n = 10) or mutant mice (n = 10) precontracted with 90 mM KCl. P < 0.001 (Ca_v1.2DHP–/– vs. WT; unpaired Student's t test). (E) Telemetric recordings (see Methods). Effects of increasing doses of BayK (left) and isradipine (right) on sinoatrial activity in vivo. R, resting, no drug. At, injection with atropine (1 mg/kg); P, injection with atropine followed by propranolol (20 mg/kg) before DHP application. Data presented as mean SEM of 4–52 experiments. *P < 0.05; **P < 0.01 for heart rate inhibition in the presence of drug (one-sample Student's t test).