Loading…
Functional Modulation of Sarcolemmal K ATP Channels by Atrial Natriuretic Peptide-Elicited Intracellular Signaling in Adult Rabbit Ventricular Cardiomyocytes
ATP-sensitive potassium (K ) channels couple cell metabolic status to membrane excitability and are crucial for stress adaptation and cytoprotection in the heart. Atrial natriuretic peptide (ANP), a cardiac peptide important for cardiovascular homeostasis, also exhibits cytoprotective features inclu...
Saved in:
Published in: | American Journal of Physiology: Cell Physiology 2020-07, Vol.319 (1), p.C194-C207 |
---|---|
Main Authors: | , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | ATP-sensitive potassium (K
) channels couple cell metabolic status to membrane excitability and are crucial for stress adaptation and cytoprotection in the heart. Atrial natriuretic peptide (ANP), a cardiac peptide important for cardiovascular homeostasis, also exhibits cytoprotective features including protection against myocardial ischemia-reperfusion injuries. However, how ANP modulates cardiac K
channels is largely unknown. In the present study we sought to address this issue by investigating the role of ANP signaling in functional modulation of sarcolemmal K
(sarcK
) channels in ventricular myocytes freshly isolated from adult rabbit hearts. Single-channel recordings were performed in combination with pharmacological approaches in the cell-attached patch configuration. Bath application of ANP markedly potentiated sarcK
channel activities induced by metabolic inhibition with sodium azide, whereas the K
-stimulating effect of ANP was abrogated by selective inhibition of the natriuretic peptide receptor type A (NPR-A), cGMP-dependent protein kinase (PKG), reactive oxygen species (ROS), extracellular signal-regulated protein kinase (ERK)1/2, Ca
/calmodulin-dependent protein kinase II (CaMKII), or the ryanodine receptor (RyR). Blockade of RyRs also nullified hydrogen peroxide (H
O
)-induced stimulation of sarcK
channels in intact cells. Furthermore, single-channel kinetic analyses revealed that ANP enhanced the function of ventricular sarcK
channels through destabilizing the long closures and facilitating the opening transitions, without affecting the single-channel conductance. In conclusion, here we report that ANP positively modulates the activity of ventricular sarcK
channels via an intracellular signaling mechanism consisting of NPR-A, PKG, ROS, ERK1/2, CaMKII and RyR2. This novel mechanism may regulate cardiac excitability and contribute to cytoprotection, in part, by opening myocardial K
channels. |
---|---|
ISSN: | 0363-6143 1522-1563 |
DOI: | 10.1152/ajpcell.00409.2019 |