Angiotensin II activation of a chloride current in rabbit cardiac myocytes.

Abstract

1. The effects of angiotensin II (Ang II) on membrane currents were investigated in single ventricular myocytes from the rabbit heart by the whole-cell voltage-clamp method. 2. In the presence of an inhibitor of Ca2+ currents (nifedipine at 3 ,UM or CdCl2 at 0 3 mM) and a f6-adrenoceptor blocker (bupranolol at 1 /LM), 1 /uM Ang II significantly increased the membrane conductance.3. After elimination of K+ from external and internal solutions and its replacement by Cs+, Ang II at 041 /M increased an outwardly rectifying current that reached a maximum after about 40 min. The effect was concentration dependent (10-9_10-6 M) and was inhibited by saralasin, an antagonist of Ang II receptors.4. The reversal potential of the Ang II-induced current in the absence of K+ was compatible with the CF_ equilibrium potential at various external concentrations of CF-.5. A Cl-channel blocker, 4,4'-dinitrostilbene-2,2'-disulphonic acid (DNDS, at 5 mM), reversibly decreased the Ang II-induced current. 6. The Ang II-induced current developed when the internal solution contained Ca2+ (pCa 7 2 or 7 0) but not when it contained 10 mm EGTA without Ca2+.7. Besides developing a Cl-current, Ang II at 1 ,UM increased the inwardly rectifying K+ current (IK1) and this effect reached maximum within 3 min. 8. The effect of Ang II on the action potential was biphasic: the duration of the action potential was initially reduced and then it was increased. 9. These results suggest that Ang II induces a Cl-current that appears likely to modulate the action potential in rabbit ventricular myocytes.

Specific role for the extracellular signal-regulated kinase pathway in angiotensin II- but not phenylephrine-induced cardiac hypertrophy in vitro

“…Compared to phenylephrine, angiotensin II increased [ 14 C]phenylalanine incorporation less efficiently. Moreover, the concentration required to significantly stimulate protein synthesis (1 µM) was high compared to other physiological effects of angiotensin II, such as contraction [13], the induction of TGF-β expression [27], and the activation of chloride channels [12]. We conclude from the comparison of the concentration-response curves that the role of angiotensin II during the generation of myocardial hypertrophy is not a main effect on cardiac growth.…”

Effects of Angiotensin II on the Action Potential Durations of Atrial Myocytes in Hypertensive Rats

“…In rabbit sinoatrial node cells, Ang II depolarized the RMPs accompanied by a reduction of the action potential amplitude and a negative chronotropic effect (23). In isolated rabbit ventricular myocytes, Morita et al (24) reported that Ang II decreased the APD after 3 min of application, but prolonged the APD after application for 7 min. These reports indicated that Ang II prolongation of the atrial and ventricular APDs was accompanied by membrane depolarization.…”

What Causes Sudden Death in Heart Failure?

“…118 Angiotensin II inhibits a number of K currents, including the Ca 2ϩ -activated K current in vascular smooth muscle cells, 119 the transient outward K current (I to1 ), 116 and delayed rectifier K currents in the heart and smooth muscle. 120 -125 Other direct effects of angiotensin II on cardiac membrane transport include increasing chloride current 112 and decreasing electrogenic Na ϩ -K ϩ ATPase. 126 The function of a number of ion channels and electrogenic transporters are regulated by aldosterone.…”