Si. Koumi et Ja. Wasserstrom, ACETYLCHOLINE-SENSITIVE MUSCARINIC K+ CHANNELS IN MAMMALIAN VENTRICULAR MYOCYTES, The American journal of physiology, 266(5), 1994, pp. 80001812-80001821
Acetylcholine (ACh) is known to increase K+ conductance in the atrium
and in pacemaker tissues in the heart. This effect has not been well d
efined in mammalian ventricular tissues. We have identified and charac
terized the ACh-sensitive muscarinic K+ channel [I-K(ACh)] activity in
isolated human, cat, and guinea pig ventricular myocytes using the pa
tch-clamp technique. Application ofACh increased whole cell membrane c
urrent in human ventricular myocytes. Current-voltage relationship of
the ACh-induced current in ventricle exhibited inward-rectification wh
ose slope conductance was smaller than that in atrium. In single-chann
el recording from cell-attached patches, I-K(ACh) activity was observe
d when ACh was included in the solution. The channel exhibited a slope
conductance of 43 +/- 2 pS. Open times were distributed according to
a single exponential function with mean open lifetime of 1.8 +/- 0.3 m
s. The channel had conductance and kinetic characteristics similar to
human atrial I-K(ACh), which had a slope conductance of 43 +/- 3 pS an
d mean open lifetime of 1.6 +/- 0.3 ms. However, concentration of ACh
at half-maximal stimulation (K-D) of the channel in ventricle was grea
ter (K-D = 0.13 mu M) than that in atrium (K-D = 0.03 mu M). Adenosine
caused activation of the same K+ channel. After formation of an excis
ed inside-out patch, channel activity disappeared. Application of GTP
(100 mu M) or GTP gamma S (100 mu M) to the solution caused reactivati
on of the channel. When myocytes were preincubated with pertussis toxi
n (PTX), ACh failed to activate these channels, indicating that the PT
X-sensitive G protein, G(i), is essential for activation of I-K(ACh).
I-K(ACh) channel activity was also found in cat and guinea pig ventric
ular myocytes. We conclude that ACh directly activates the I-K(ACh) in
mammalian ventricular myocytes via Gi in a fashion almost identical t
o atrial myocytes.