Modulation of cardiac Na channels by angiotensin II.
The modulation of Na channels by the vasoactive peptide angiotensin II (AT II) has been studied in isolated ventricular cells of guinea pigs using the patch clamp technique. In cell-attached patches the maximal probability of the channel being open was increased in a concentration range between 0.05 and 1 microM, but decreased at higher concentrations. A maximal increased of 2.5 +/- 0.86 was found at 1 microM AT II. The increase in the probability of the channel being open was due to a decrease in the number of nulls. In all affected cells (n = 17) we observed a delayed inactivation after application of AT II at concentrations between 0.05 and 10 microM. At -30 mV, the time constant of inactivation increased from 1.1 +/- 0.1 ms (controls) to 5.6 +/- 1.6 ms (10 microM AT II). This effect was due to an increased number of openings per sweeps. No significant effect on the mean open time and the first latency were observed. However, due to pronounced bursting, the averaged closed time was significantly increased from 0.8 +/- 0.1 ms to 1.3 +/- 0.1 ms in the presence of 1 microM AT II at -30 mV. An effect of AT II on cardiac Na channels via protein kinase C is discussed.
Nilius
B
B
Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, G.D.R.
Tytgat
J
J
Albitz
R
R
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004566:Electrodes; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology
D015222:Sodium Channels; D000804:Angiotensin II; D001224:Aspartic Acid