Involvement of Na(+)-H+ antiporter in regulation of L-type Ca2+ channel current by angiotensin II in rabbit ventricular myocytes.
The present study investigated the possible involvement of a Na(+)-H+ antiporter in the regulation of L-type Ca2+ channels by angiotensin II (Ang II) in isolated rabbit ventricular cardiac myocytes by using both cell-attached and whole-cell patch-clamp current recording techniques. In cell-attached patch-clamp current recordings, an increase in the open-state probability of the Ca2+ channel (144.8 +/- 9.8% [mean +/- SEM], n = 11) was seen after exposure of the cells to Ang II (100 nmol/L). This effect was inhibited by pretreatment with losartan (10 mumol/L), a synthetic antagonist of the AT1 receptor. 5(N,N-Dimethyl)amiloride (100 mumol/L), an amiloride analogue, as well as Na(+)-deficient bath solution abolished Ang II-induced stimulation of the Ca2+ channel activities. In whole-cell patch-clamp current recordings, Ang II also increased the L-type Ca2+ current when a pipette solution of pH 7.1 containing 5 mmol/L HEPES (139 +/- 5%, n = 4) was used but did not significantly increase the current when a pipette solution of pH 7.5 containing 5 mmol/L HEPES or a pipette solution of pH 7.1 containing 30 mmol/L HEPES was used. These results suggest that Ang II-induced stimulation of the Ca2+ channels is mediated by a Na(+)-H+ antiporter and therefore provide a novel insight into signal transduction of Ang II receptor stimulation in cardiac myocytes.
Third Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
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M
Kaibara
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S
Mitarai
K
K
Yano
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M
Kameyama
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016276:Ventricular Function
D015220:Calcium Channels; D011945:Receptors, Angiotensin; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II