Projects per year
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.
Original language | English |
---|---|
Pages (from-to) | 61-74 |
Number of pages | 14 |
Journal | Pflugers Archiv European Journal of Physiology |
Volume | 472 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2020 |
Fingerprint
Dive into the research topics of 'Neuronal nitric oxide synthase regulation of calcium cycling in ventricular cardiomyocytes is independent of Cav1.2 channel modulation under basal conditions'. Together they form a unique fingerprint.Projects
- 2 Finished
-
The L-type calcium channel in cardiovascular health and disease
Hool, L. (Investigator 01)
NHMRC National Health and Medical Research Council
1/01/17 → 31/12/21
Project: Research
-
A novel therapy for the prevention and treatment of familial hypertrophic cardiomyopathy
Hool, L. (Investigator 01), Semsarian, C. (Investigator 02) & Swaminatha Iyer, I. (Investigator 03)
NHMRC National Health and Medical Research Council
1/01/16 → 31/12/20
Project: Research