Characterization of the acetylcholine-sensitive muscarinic K+ channel in isolated feline atrial and ventricular myocytes |
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| Authors: | S -i. Koumi R. Sato H. Hayakawa |
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| Affiliation: | (1) Department of Medicine, Northwestern University Medical School, 60611 Chicago, IL, USA;(2) Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 60611 Chicago, IL, USA;(3) First Department of Medicine, Nippon Medical School, 113 Tokyo, Japan;(4) First Department of Medicine, Kinki University School of Medicine, 589 Osaka, Japan |
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| Abstract: | M2-cholinergic receptor activation by acetylcholine (ACh) is known to cause a negative inotropic and chronotropic action in atrial tissues. This effect is still controversial in ventricular tissues. The ACh-sensitive muscarinic K+ channel (IK(ACh)) activity was characterized in isolated feline atrial and ventricular myocytes using the patch-clamp technique. Bath application of ACh (1  m) caused shortening of action potential duration without prior stimulation with catecholamines in atrial and ventricular myocytes. Resting membrane potential was slightly hyperpolarized in both tissues. These effects of ACh were greater in atrium than in ventricle. ACh increased whole-cell membrane current in atrial and ventricular myocytes. The current-voltage (I-V) relationship of the ACh-induced current in ventricle exhibited inward-rectification whose slope conductance was smaller than that in atrium. In single channel recording from cell-attached patches, IK(ACh) activity was observed when ACh was induced in the pipette solution in both tissues. The channel exhibited a slope conductance of 47 ±1 pS (mean ± sd, n=14) in atrium and 47 ±2 pS (n= 10) in ventricle (not different statistically; ns). The open times were distributed according to a single exponential function with mean open lifetime of 2.0±0.3 msec (n= 14) in atrium and 1.9±0.3 msec (n=10) in ventricle (ns); these conductance and kinetic properties were similar between the two tissues. However, the relationship between the concentration of ACh and single channel activity showed a higher sensitivity to ACh in atrium (IC50=0.03 m) than in ventricle (IC50=0.15 m). In excised inside-out patches, ventricular IK(ACh) required higher concentrations of GTP to activate the channel compared to atrial channels. These results suggest a reduced IK(ACh) channel sensitivity to M2-cholinergic receptor-linked G protein (Gi) in ventricle compared to atrium in feline heart. |
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| Keywords: | Patch clamp technique Acetylcholine Muscarinic K+ channel GTP — G protein |
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