Acetylcholine activates an inward current in single mammalian smooth muscle cells

Abstract

Acetylcholine, the major excitatory neurotransmitter to the smooth muscle of mammalian intestine, is known to depolarize smooth muscle cells with an apparent increase in membrane conductance. However, the ionic mechanisms that are triggered by muscarinic receptor activation and underlie this response are poorly understood, due in part to the technical problems associated with the electrophysiological study of smooth muscle. The muscarinic action of acetylcholine in certain neurones has been shown to involve the switching off of a resting K+ current (M-current) and a similar mechanism has recently also been identified in smooth muscle of amphibian stomach. We have now applied the patch-clamp technique to single smooth muscle cells of rabbit jejunum and find that muscarinic receptor activation switches on a nonselective, voltage-sensitive inward current. In addition, acetylcholine activates and then suppresses spontaneous K+ current transients, which are probably triggered by rises in intracellular Ca2+ in these cells.

G Protein-independent Activation of an Inward Na+Current by Muscarinic Receptors in Mouse Pancreatic β-Cells

“…Such channels are clearly not responsible for the AChinduced inward current in ␤-cells because the muscarinic antagonist atropine completely prevented the current and the rise in [Na ϩ ] c (15), whereas the ACh-activated current was not mimicked by nicotine and was insensitive to nicotinic antagonists. Activation of a Na ϩ conductance by muscarinic receptors is unusual but has occasionally been reported in cardiac myocytes (30,31), smooth muscle cells of the gastro-intestinal tract (32,33), chromaffin cells (34), and Chinese hamster ovary cells expressing M 3 receptors (35).…”

Modulation of carbachol‐induced [Ca2+]i oscillations by Ca2+ influx in single intestinal smooth muscle cells

“…The cell variation in sensitivity to the Ca2+ channel blockers (see Figure 3) (Hashii et al, 1993;Yao & Parker, 1994). The muscarinic receptor-coupled cation channels (Benham et al, 1985;Inoue & Isenberg, 1990; (Pacaud & Bolton, 1991).…”

“…Carbachol (CCh) is capable of inducing InsP3-dependent [Ca2+], oscillations in single smooth muscle cells of guinea-pig ileum (Komori et al, 1993;Kohda et al, 1996). The present study aimed to investigate potential path- (Benham et al, 1985;Inoue & Isenberg, 1990;Komori et al, 1992) and can change its intensity in a manner closely correlated with [Ca2+]i (Pacaud & Bolton, 1991; Brifish Journal of Phamacology (1996Phamacology ( ) 119, 245 252 1993 …”

Blockade by the local anaesthetic, tetracaine, of desensitization of Ca‐induced Ca release after muscarinic stimulation in smooth muscle

“…Therefore, it appears that carbacholinduced desensitization of intracellular Ca stores and change in the K+-induced contraction occurred independently. Acetylcholine has been reported to increase intracellular Na content (Joiner, 1973) and to activate nonselective cation channels in smooth muscle cells (Benham et al, 1985;Inoue & Isenberg, 1990). Increase in intracellular Na will trigger Na/Ca exchange and the Na pump (Bolton, 1979: Brading, 1981.…”