Activation of inwardly rectifying potassium channels by muscarinic receptor-linked G protein in isolated human ventricular myocytes

Activation of inwardly rectifying potassium channels by muscarinic receptor-linked G protein in... Muscarinic receptor-linked G protein, Gi, can directely activate the specific K+ channel (I K(ach)) in the atrium and in pacemaker tissues in the heart. Coupling of Gi to the K+ channel in the ventricle has not been well defined. G protein regulation of K+ channels in isolated human ventricular myocytes was examined using the patch-clamp technique. Bath application of 1 μM acetylcholine (ACh) reversibly shortened the action potential duration to 74.4 ± 12.1% of control (at 90% repolarization, mean ± sd, n = 8) and increased the whole-cell membrane current conductance without prior β-adrenergic stimulation in human ventricular myocytes. The ACh effect was reversed by atropine (1 μm). In excised inside-out patch configurations, application of GTPγS (100 μm) to the bath solution (internal surface) caused activation of I K(ACh) and/or the background inwardlyrectifying K+ channel (I K1,) in ventricular cell membranes. I K(ACh) exhibited rapid gating behavior with a slope conductance of 44 ± 2 pS (n = 25) and a mean open lifetime of 1.8 ± 0.3 msec (n = 21). Single channel activity of GTPγS-activated I K1 demonstrated longlasting bursts with a slope conductance of 30 ± 2 pS (n = 16) and a mean open lifetime of 36.4 ± 4.1 msec (n = 12). Unlike I K(ACh)’ G protein-activated I K1 did not require GTP to maintain channel activity, suggesting that these two channels may be controlled by G proteins with different underlying mechanisms. The concentration of GTP at half-maximal channel activation was 0.22 μm in I K(ACh) and 1.2 μm in I K1. Myocytes pretreated with pertussis toxin (PTX) prevented GTP from activating these channels, indicating that muscarinic receptorlinked PTX-sensitive G protein, Gi, is essential for activation of both channels. G protein-activated channel characteristics from patients with terminal heart failure did not differ from those without heart failure or guinea pig. These results suggest that ACh can shorten the action potential by activating I K(ACh) and I K1 via muscarinic receptor-linked Gi, proteins in human ventricular myocytes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Activation of inwardly rectifying potassium channels by muscarinic receptor-linked G protein in isolated human ventricular myocytes

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Publisher
Springer Journals
Copyright
Copyright © 1997 by Springer-Verlag
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s002329900217
Publisher site
See Article on Publisher Site

Abstract

Muscarinic receptor-linked G protein, Gi, can directely activate the specific K+ channel (I K(ach)) in the atrium and in pacemaker tissues in the heart. Coupling of Gi to the K+ channel in the ventricle has not been well defined. G protein regulation of K+ channels in isolated human ventricular myocytes was examined using the patch-clamp technique. Bath application of 1 μM acetylcholine (ACh) reversibly shortened the action potential duration to 74.4 ± 12.1% of control (at 90% repolarization, mean ± sd, n = 8) and increased the whole-cell membrane current conductance without prior β-adrenergic stimulation in human ventricular myocytes. The ACh effect was reversed by atropine (1 μm). In excised inside-out patch configurations, application of GTPγS (100 μm) to the bath solution (internal surface) caused activation of I K(ACh) and/or the background inwardlyrectifying K+ channel (I K1,) in ventricular cell membranes. I K(ACh) exhibited rapid gating behavior with a slope conductance of 44 ± 2 pS (n = 25) and a mean open lifetime of 1.8 ± 0.3 msec (n = 21). Single channel activity of GTPγS-activated I K1 demonstrated longlasting bursts with a slope conductance of 30 ± 2 pS (n = 16) and a mean open lifetime of 36.4 ± 4.1 msec (n = 12). Unlike I K(ACh)’ G protein-activated I K1 did not require GTP to maintain channel activity, suggesting that these two channels may be controlled by G proteins with different underlying mechanisms. The concentration of GTP at half-maximal channel activation was 0.22 μm in I K(ACh) and 1.2 μm in I K1. Myocytes pretreated with pertussis toxin (PTX) prevented GTP from activating these channels, indicating that muscarinic receptorlinked PTX-sensitive G protein, Gi, is essential for activation of both channels. G protein-activated channel characteristics from patients with terminal heart failure did not differ from those without heart failure or guinea pig. These results suggest that ACh can shorten the action potential by activating I K(ACh) and I K1 via muscarinic receptor-linked Gi, proteins in human ventricular myocytes.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Mar 31, 2009

References

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