Short-Term Desensitization of Muscarinic K+ Current in the Heart

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Short-term desensitization of muscarinic K+ current in the heart.

Acetylcholine (ACh) rapidly increases cardiac K(+) currents (IKACh) by activating muscarinic K(+) (KACh) channels followed by a gradual amplitude decrease within seconds. This phenomenon is called short-term desensitization and its precise mechanism and physiological role are still unclear. We constructed a mathematical model for IKACh to examine the conditions required to reconstitute short-te...

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Role of receptor kinase in long-term desensitization of the cardiac muscarinic receptor-K+ channel system.

Desensitization of the cardiac muscarinic K+ channel was studied in cultured neonatal rat atrial cells and in Chinese hamster ovary (CHO) cells transfected with muscarinic receptor (HM(2)), G protein-coupled inward rectifying K+ channels 1 and 4, and G protein-coupled receptor kinase 2. In atrial cells incubated in 10 microM carbachol for 24 h, channel activity in cell-attached patches was subs...

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Evidence of involvement of GIRK1/GIRK4 in long-term desensitization of cardiac muscarinic K+ channels.

The cardiac M2 muscarinic receptor/G protein/K+ channel system was studied in neonatal rat atrial cells cultured with and without 10 microM carbachol (CCh) for 24 h. Channel activity in CCh-pretreated cells was substantially reduced as a result of long-term desensitization regardless of whether the channel was activated by ACh in cell-attached patches or GTP in inside-out patches. Channel activ...

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Muscarinic K+ Channel in the Heart

The membrane-delimited activation of muscarinic K+ channels by G protein beta gamma subunits plays a prominent role in the inhibitory synaptic transmission in the heart. These channels are thought to be heterotetramers comprised of two homologous subunits, GIRK1 and CIR, both members of the family of inwardly rectifying K+ channels. Here, we demonstrate that muscarinic K+ channels in neonatal r...

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ژورنال

عنوان ژورنال: Biophysical Journal

سال: 2013

ISSN: 0006-3495

DOI: 10.1016/j.bpj.2013.08.009