Effects of ACh and adenosine mediated by Kir3.1 and Kir3.4 on ferret ventricular cells.
The inotropic effects of ACh and adenosine on ferret ventricular cells were investigated with the action potential-clamp technique. Under current clamp, both agonists resulted in action potential shortening and a decrease in contraction. Under action potential clamp, both agonists failed to decrease contraction substantially. In the absence of agonist, application of the short action potential waveform (recorded previously in the presence of agonist) also resulted in a decrease in contraction. Under action potential clamp, application of ACh resulted in a Ba(2+)-sensitive outward current with the characteristics of muscarinic K+ current (I(K,ACh)); the presence of the muscarinic K+ channel was confirmed by PCR and immunocytochemistry. In the absence of agonist, on application of the short ACh action potential waveform, the decrease in contraction was accompanied by loss of the inward Na(+)/Ca(2+) exchange current (I(NaCa)). ACh also inhibited the background inward K+ current (I(K,1)). It is concluded that ACh activates I(K,ACh), inhibits I(K,1), and indirectly inhibits I(NaCa); this results in action potential shortening, decrease in contraction, and, as a result of the inhibition of I(K,1), minimum decrease in excitability.
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.
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Dobrzynski
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Janvier
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Leach
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JB
Findlay
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MR
Boyett
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D005289:Ferrets; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006325:Heart Atria; D006352:Heart Ventricles; D008954:Models, Biological; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D000241:Adenosine; D000109:Acetylcholine