Ebner, Janine and Cagalinec, Michal and Kubista, Helmut and Todt, Hannes and Szabo, Petra L. and Kiss, Attila and Podesser, Bruno K. and Cserne Szappanos, Henrietta and Hool, Livia C. and Hilber, Karlheinz and Koenig, Xaver (2020) Neuronal nitric oxide synthase regulation of calcium cycling in ventricular cardiomyocytes is independent of Cav1.2 channel modulation under basal conditions. Pflügers Archiv - European Journal of Physiology. ISSN 0031-6768
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Abstract
Neuronal nitric oxide synthase (nNOS) is considered a regulator of Cav1.2 L-type Ca2+ channels and downstream Ca2+ cycling in the heart. The commonest view is that nitric oxide (NO), generated by nNOS activity in cardiomyocytes, reduces the currents through Cav1.2 channels. This gives rise to a diminished Ca2+ release from the sarcoplasmic reticulum, and finally reduced contractility. Here, we report that nNOS inhibitor substances significantly increase intracellular Ca2+ transients in ventricular cardiomyocytes derived from adult mouse and rat hearts. This is consistent with an inhibitory effect of nNOS/NO activity on Ca2+ cycling and contractility. Whole cell currents through L-type Ca2+ channels in rodent myocytes, on the other hand, were not substantially affected by the application of various NOS inhibitors, or application of a NO donor substance. Moreover, the presence of NO donors had no effect on the single-channel open probability of purified human Cav1.2 channel protein reconstituted in artificial liposomes. These results indicate that nNOS/NO activity does not directly modify Cav1.2 channel function. We conclude that-against the currently prevailing view-basal Cav1.2 channel activity in ventricular cardiomyocytes is not substantially regulated by nNOS activity and NO. Hence, nNOS/NO inhibition of Ca2+ cycling and contractility occurs independently of direct regulation of Cav1.2 channels by NO.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 07 Jan 2020 22:27 |
| Last Modified: | 12 Oct 2021 03:31 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/907 |
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