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Natriuretic peptides modulate ATP-sensitive K+ channels in rat ventricular cardiomyocytes

Burley, Dwaine, Cox, Charles D., Zhang, Jin, Wann, Kenneth T. and Baxter, Gary F. ORCID: 2014. Natriuretic peptides modulate ATP-sensitive K+ channels in rat ventricular cardiomyocytes. Basic Research in Cardiology 109 , 402. 10.1007/s00395-014-0402-4

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B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and (Cys-18)-atrial natriuretic factor (4–23) amide (C-ANF), are cytoprotective under conditions of ischemia–reperfusion, limiting infarct size. ATP-sensitive K+ channel (KATP) opening is also cardioprotective, and although the KATP activation is implicated in the regulation of cardiac natriuretic peptide release, no studies have directly examined the effects of natriuretic peptides on cardiac KATP activity. Normoxic cardiomyocytes were patch clamped in the cell-attached configuration to examine sarcolemmal KATP (sKATP) activity. The KATP opener pinacidil (200 μM) increased the open probability of the patch (NPo; values normalized to control) at least twofold above basal value, and this effect was abolished by HMR1098 10 μM, a selective KATP blocker (5.23 ± 1.20 versus 0.89 ± 0.18; P < 0.001). We then examined the effects of BNP, CNP, C-ANF and 8Br-cGMP on the sKATP current. Bath application of BNP (≥10 nM) or CNP (≥0.01 nM) suppressed basal NPo (BNP: 1.00 versus 0.56 ± 0.09 at 10 nM, P < 0.001; CNP: 1.0 versus 0.45 ± 0.16, at 0.01 nM, P < 0.05) and also abolished the pinacidil-activated current at concentrations ≥10 nM. C-ANF (≥10 nM) enhanced KATP activity (1.00 versus 3.85 ± 1.13, at 100 nM, P < 0.05). The cGMP analog 8Br-cGMP 10 nM dampened the pinacidil-activated current (2.92 ± 0.60 versus 1.53 ± 0.32; P < 0.05). Natriuretic peptides modulate sKATP current in ventricular cardiomyocytes. This may be at least partially associated with their ability to augment intracellular cGMP concentrations via NPR-A/B, or their ability to bind NPR-C with high affinity. Although the mechanism of modulation requires elucidation, these preliminary data give new insights into the relationship between natriuretic peptide signaling and sKATP in the myocardium.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: Natriuretic peptides; cardiomyocytes; electrophysiology; Ion channels.
Additional Information: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
Publisher: Springer Verlag (Germany)
ISSN: 0300-8428
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 10 January 2014
Last Modified: 25 Oct 2022 09:57

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