Angiotensin II Receptor Regulates Ionic Currents in Guinea Pig Ventricular Myocytes.
BACKGROUND: Previous studies have shown that angiotensin II (Ang II) receptors are preset in a wide variety of target tissues and that Ang II regulates the target tissue functions through Ang II receptors. However, the action of Ang II receptors on transsarcolemmal currents in ventricular myocytes has not been elucidated. METHODS AND RESULTS: We performed whole-cell voltage clamp and patch clamp experiments to determine the effects of Ang II-receptor agonists and antagonists on ionic currents in single isolated guinea pig ventricular myocytes. We found that extracellular perfusion of Ang II (30 nM) increased the L-type Ca(2+) current from 581 +/- 27 to 837 +/- 42 pA (n = 5, P <.01). Ang II also prolonged the Ca(2+) current activation and inactivation time constants. These were reversible by losartan (100 nM), a type 1 Ang II receptor (AT(1)) blockade. On the other hand, perfusion of 30 nM Ang II decreased K(+) current (I(K)) from 1543 +/- 28 to 1194 +/- 50 pA (n = 5, P <.05) and K(+) tail current (I(K-tail)) from 275 +/- 24 to 206 +/- 29 pA (n = 5, P <.05). These effects were also abolished by perfusion of losartan. However, perfusion of Ang II resulted in an increase of inward rectified K(+) current (I(K1)) in whole-cell recordings. Single channel recordings showed that the increase in I(K1) was attributed to a burst opening current with a larger unit of amplitude. These effects were reversed by saralasin but not losartan, indicating possible type 2 Ang II receptor (AT(2)) involvement. CONCLUSIONS: Our results provide evidence that Ang II receptors regulate the transsarcolemmal currents in single guinea pig ventricular myocytes. Therefore, Ang II regulation of ionic currents is mediated through the different subtypes of Ang II receptors.
Yang
Xj
Laboratory of Cardiology, Suzhou, P.R. China
Jiang
Wp