Muscarinic inhibitory and stimulatory regulation of the L-type Ca2+ current is not altered in cardiac ventricular myocytes from mice lacking endothelial nitric oxide synthase

被引:46
作者
Belevych, AE [1 ]
Harvey, RD [1 ]
机构
[1] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2000年 / 528卷 / 02期
关键词
D O I
10.1111/j.1469-7793.2000.00279.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. Using conventional and perforated patch-clamp techniques, the inhibitory and stimulatory effects of acetylcholine (ACh) on beta -adrenergic regulation of the L-type Ca2+ current (I-Ca) were studied in ventricular myocytes from wild-type mice (WT) and from mice lacking endothelial nitric oxide synthase (eNOS, or NOS3; NOS3-KO mice). 2. To validate the direct comparison of ACh effects on beta -adrenergic responses, the sensitivity of I-Ca to the beta -adrenergic agonist isoprenaline (Iso) was studied in both WT and NOS3-KO mouse myocytes. I-Ca sensitivity to Iso was not found to be significantly different in WT and NOS3-KO myocytes: Iso increased I-Ca with an EC50 of 4.9 and 3.7 nM in WT and NOS3-KO myocytes, respectively. 3. ACh-induced inhibition of I-Ca did not significantly differ in ventricular myocytes from WT and NOS3-KO mice. ACh (10 muM) inhibited the stimulatory effect of 3 nM Iso by 39 and 35% in WT and NO83-KO myocytes, respectively. 4. Exposure to and subsequent washout of ACh in the continuous presence of submaximally stimulating concentrations of Iso (1-3 nM) resulted in a transient rebound stimulation of I-Ca in both WT and NOS3-KO mouse myocytes. The magnitude of the stimulatory effect of ACh did not significantly differ in WT and NOS3-KO mice. 5. These results indicate that nitric oxide (NO) generated by NOS3 does not significantly affect the beta -adrenergic responsiveness of I-Ca. The results also confirm previous work indicating that NO generated by NOS3 is not obligatory for muscarinic inhibition of the beta -adrenergically regulated I-Ca in ventricular myocytes. Finally these results demonstrate for the first time that NO generated by NOS3 is not involved in muscarinic rebound stimulation of I-Ca in ventricular myocytes.
引用
收藏
页码:279 / 289
页数:11
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