MODE OF REGULATION OF THE ACH-SENSITIVE K-CHANNEL BY THE MUSCARINIC RECEPTOR IN RABBIT ATRIAL CELLS
MODE OF REGULATION OF THE ACH-SENSITIVE K-CHANNEL BY THE MUSCARINIC RECEPTOR IN RABBIT ATRIAL CELLS
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DOI：
10.1007/bf00587544
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发表时间：
1984-01-01
影响因子：
4.5
通讯作者：
NOMA, A
中科院分区：
文献类型：
--
作者：
SOEJIMA, M;NOMA, A
The mechanism underlying the regulation of the K-channel by the muscarinic receptor was examined with patch-clamp experiments in atrial cells isolated enzymatically from the rabbit heart. The patch-electrode and the recording chamber were perfused with various solutions while the activity of the K-channels in the membrane-patch was recorded continuously. In the absence of muscarinic agonists, opening of K-channels occurred at a low frequency (basal activity). Application of ACh [acetylcholine] to the bath did not affect the basal activity, but perfusion of the patch-electrode with ACh markedly increased the channel activity in the cell-attached patch. Application of oxotremorine, i.e., a specific muscarinic agonist, via the pipette also opened K-channels. When the membrane patch was isolated from the cell body (inside-out patch), ACh-induced single K-channel currents were still observed, but the frequency was reduced. Perfusion of atropine or scopolamine, 2 muscarinic antagonists, through the patch-electrode depressed the basal activity. In the case of scopolamine, channel-activity recovered after washing out the drug. The current-voltage relationship determined from the basal activity was similar to that of ACh-induced single K-channel currents. The mean open time was 0.49 ms at basal activity and 1.35 ms during the application of 0.1 .mu.M ACh via the patch electrode. Application of oxotremorine via the pipette hardly affected the open-time, it remained at 99 .+-. 4% (n = 7) of the control. The ACh-induced K current evidently is generated by a class of K-channels having open and close kinetics. The ACh-muscarinic receptor-complex directly increases the probability of this K-channel being open by coupling with the channel. The increase in open-state probability is mainly due to shortening of the mean closed-time; basal activity is most probably generated by this K-channel. Muscarinic antagonists depress the ACh-induced K-current not only by blocking the binding of the agonist to the receptor, but also through a depressing influence of the antagonist-receptor-complex on the K-channel.
