Angiotensin II type 1 receptor modulation of L-type calcium currents in guinea-pig ventricular cells

Objective To study the cellular mechanism of the effect of Ang II on lca,L in single guinea-pig ventricular cells by using losartan and 1-( 5-lsoquino linylsulfonyl)-2-Methyl-Piperazine (H-7) as the Ang II type 1 receptor (AT 1) inhibitor and protein kinase C inhibitor, respectively. Methods Patch clamp techniques were used to study the cellular mechanism of the effect of Ang II on I-Ca,I-L in single guinea-pig ventricular cells. Results In the whole cell patch clamp recording model, Ang II stimulated IC a,L in a concentration dependent manner; the maximal effect was obtained at 100 nmol/L (n = 9). At 30 nmol/L, Ang IE stimulated peak I-Ca,I-L from 11. 3 +/- 0.6 pA/pF to 15.3 +/- 0.6 pA/pF (at + 10 mV, n = 9, P < 0.05). 100 nm ol/L Losartan, a specific AT, receptor inhibitor, had no effect on I-Ca,I-L (n = 9), but the effect of Ang II on I-Ca,I-L was inhibited by 100 nmol/L L osartan. Ang II on I-Ca,I-L was also inhibited by 20 mu mol/L H-7, a specif ic protein kinase C inhibitor, whereas H-7 alone has no effect on I-Ca,I-L( n = 9). Conclusion Ang II stimulates I-Ca,I-L in guinea-pig ventricular cells by bi nding to AT1 through a transduction pathway involving protein kinase C.