Membrane stretch augments the cardiac muscarinic K+ channel activity.
Arachidonic acid has been shown to activate K(+)-selective, mechanosensitive ion channels in cardiac, neuronal and smooth muscle cells. Since the cardiac G protein (GK)-gated, muscarinic K+ (KACh) channel can also be activated by arachidonic acid, we investigated whether the KACh channel was also sensitive to membrane stretch. In the absence of acetylcholine (ACh), KACh channels were not active, and negative pressure failed to activate these channels. With ACh (10 microM) in the pipette, applying negative pressure (0 to -80 mm Hg) to the membrane caused a reversible, pressure-dependent increase in channel activity in cell-attached and inside-out patches (100 microM GTP in bath). Membrane stretch did not alter the sensitivity of the KACh channel to GTP. When GK was maximally activated with 100 microM GTP gamma S in inside-out patches, the KACh channel activity could be further increased by negative pressure. Trypsin (0.5 mg/ ml) applied to the membrane caused activation of the KACh channel in the absence of ACh and GTP; KACh channel activity was further increased by stretch. These results indicate that the atrial muscarinic K+ channels are modulated by stretch independently of receptor/G protein, probably via a direct effect on the channel protein/ lipid bilayer.
Pleumsamran
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A
Department of Physiology and Biophysics, Finch University of Health Sciences Chicago Medical School, IL 60064, USA.
Kim
D
D
D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013314:Stress, Mechanical; D014357:Trypsin / Q000494:pharmacology
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D014357:Trypsin; D019204:GTP-Binding Proteins; D000109:Acetylcholine