gramicidin-a and candesartan

The effects of angiotensin II (Ang II) on L-type Ca2+ current (I(Ca,L)) remains controversial. We studied the effects of Ang II on I(Ca,L) in single adult rabbit ventricular myocytes using a perforated patch-clamp technique with gramicidin D. Ang II increased I(Ca,L) in a concentration-dependent manner (EC(50)=0.75 nM). In contrast, in conventional whole-cell patch-calmp, I(Ca,L)ran down gradually and the I(Ca,L) response to Ang II was variable, suggesting the potential loss of diffusible components crucial for the Ang II-induced signaling process. An AT(1) antagonist, CV11974 (0.1 microM), completely inhibited the increase in I(Ca,L) induced by Ang II (0.1 microM), whereas an AT(2) antagonist, PD123319 (10 microM), did not influence the I(Ca,L) increase. Neither pre- nor after-treatment with a Na+/H+ exchange (NHE) inhibitor HOE642 (1 microM) affected the Ang II-induced increase in I(Ca,L). The protein kinase C (PKC) inhibitor chelerythrine (1 microM) did not affect the Ang II-induced I(Ca,L) increase. The present findings indicate that Ang II increases I(Ca,L) via AT(1) receptors in adult rabbit ventricular myocytes. Neither the activation of NHE nor PKC may contribute to the Ang II-induced activation of I(Ca,L).

Topics: Action Potentials; Alkaloids; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Anti-Bacterial Agents; Benzimidazoles; Benzophenanthridines; Biphenyl Compounds; Calcium Channels, L-Type; Cell Separation; Electrophysiology; Enzyme Inhibitors; Gramicidin; Guanidines; Heart; Heart Ventricles; In Vitro Techniques; Male; Myocardium; Patch-Clamp Techniques; Phenanthridines; Protein Kinase C; Rabbits; Receptor, Angiotensin, Type 1; Sodium-Hydrogen Exchangers; Sulfones; Tetrazoles