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Neuronal nitric oxide synthase regulation of calcium cycling in ventricular cardiomyocytes is independent of Ca_v1.2 channel modulation under basal conditions.

ABSTRACT: Neuronal nitric oxide synthase (nNOS) is considered a regulator of Ca_v1.2 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 Ca_v1.2 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 Ca_v1.2 channel protein reconstituted in artificial liposomes. These results indicate that nNOS/NO activity does not directly modify Ca_v1.2 channel function. We conclude that-against the currently prevailing view-basal Ca_v1.2 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 Ca_v1.2 channels by NO.

SUBMITTER: Ebner J

PROVIDER: S-EPMC6960210 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Neuronal nitric oxide synthase regulation of calcium cycling in ventricular cardiomyocytes is independent of Cav1.2 channel modulation under basal conditions.

Ebner Janine J Cagalinec Michal M Kubista Helmut H Todt Hannes H Szabo Petra L PL Kiss Attila A Podesser Bruno K BK Cserne Szappanos Henrietta H Hool Livia C LC Hilber Karlheinz K Koenig Xaver X

Pflugers Archiv : European journal of physiology 20191210 1

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 significan ...[more]

PMID: 31822999

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Dataset Information

Neuronal nitric oxide synthase regulation of calcium cycling in ventricular cardiomyocytes is independent of Ca_v1.2 channel modulation under basal conditions.

Publications

Neuronal nitric oxide synthase regulation of calcium cycling in ventricular cardiomyocytes is independent of Ca<sub>v</sub>1.2 channel modulation under basal conditions.

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