CHARACTERIZATION OF THE ACETYLCHOLINE-SENSITIVE MUSCARINIC K+ CHANNELIN ISOLATED FELINE ATRIAL AND VENTRICULAR MYOCYTES

M(2)-cholinergic receptor activation by acetylcholine (ACh) is known t o cause a negative inotropic and chronotropic action in atrial tissues . This effect is still controversial in ventricular tissues. The ACh-s ensitive muscarinic K+ channel (I-K(ACh) activity was characterized in isolated feline atrial and ventricular myocytes using the patch-clamp technique. Bath application of ACh (1 mu M) caused shortening of acti on potential duration without prior stimulation with catecholamines in atrial and ventricular myocytes. Resting membrane potential was sligh tly 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) relatio nship of the ACh-induced current in ventricle exhibited inward-rectifi cation whose slope conductance was smaller than that in atrium. In sin gle channel recording from cell-attached patches, (I-K(ACh) activity w as observed when ACh was induced in the pipette solution in both tissu es. The channel exhibited a slope conductance of 47 +/- 1 pS (mean +/- so, n = 14) in atrium and 47 +/- 2 pS (n = 10) in ventricle (not diff erent statistically; Na). 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 t wo tissues. However, the relationship between the concentration of ACh and single channel activity showed a higher sensitivity to ACh in atr ium (IC50 = 0.03 mu M) than in ventricle (IC50 = 0.15 mu M). In excise d inside-out patches, ventricular I-K(ACh) required higher concentrati ons of GTP to activate the channel compared to atrial channels. These results suggest a reduced I-K(ACh) channel sensitivity to M(2)-choline rgic receptor-linked G protein (G(i)) in ventricle compared to atrium in feline heart.