Nonselective Cation Channels Activated by the Stimulation of Muscarinic Receptors in Mammalian Gastric Smooth Muscle
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概要
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Muscarinic receptors play key roles in the control of gastrointestinal smooth muscle activity. However, specific physiological functions of each subtype remain to be determined. Single cell RT-PCR experiments showed that all five subtypes of muscarinic receptors were present in circular smooth muscle cells of the guinea-pig gastric antrum. Nonselective cation channels (NSCC) activated by ACh or CCh are coupled to pertussis toxin (PTX)-sensitive Go protein through m4 subtype as well as m2 and m3 subtypes in guinea-pig stomach. CCh-activated currents (I_<CCh>), especially the steady-state I-V relationship of I_<CCh> showed a chracteristic U-shaped curve; reversal potential of around 0 mV and inward rectification at around +15 mV and a negative slope conductance at negative potential range. Under physiological conditions, the measured single channel conductance of NSCC was approximately 25 pS. The single channel conductance was modulated by external monovalent and divalent cations including Na^+, Cs^+, Li^+, and Ca^<2+> through changing both the open probability and unitary conductance. Through the NSCC, Ca^<2+> can move into the cell from extracellular solution as well as Na^+. Calculated fractional Ca^<2+> current of I_<CCh> (f_<Ca>) was around 1% at the 2 mM [Ca^<2+>]_0 and at the 4 mM [Ca^<2+>]_0, f_<Ca> was 2.3%. Quinidine blocked I_<CCh> potently in a reversible manner; IC_<50> was 0.25 μM. There were two kinds of I_<CCh> modulations through Ca^<2+>-dependent pathways in guinea-pig gastric smooth muscle cells; 1) Facilitation of I_<CCh> via Ca^<2+>/CaM-dependent MLCK pathway, 2) Desensitization of I_<CCh> via Ca^<2+>-dependent PKC pathway. In the mouse stomach, all seven types of TRPC mRNA were detected with RT-PCR. On the basis of electrophysiological, pharmacological, and molecular biological experiments, we reported the mTRPCS as a candidate for the NSCC activated by muscarinic stimulation in mouse stomach.
- 日本平滑筋学会の論文
著者
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Kim Ki
Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Oral Science Res
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So Insuk
Department of Physiology, Seoul National University College of Medicine
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Kim Ki
韓国
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Kim K
Department Of Physiology School Of Medicine Gachon University Of Medicine And Science
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So Insuk
Department Of Physiology Seoul National University College Of Medicine
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So I
Department Of Physiology And Biophysics Seoul National University College Of Medicine
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So Insuk
Department Of Physiology And Biophysics Seoul National University College Of Medicine
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Kim Ki
Department Of Physiology School Of Medicine Gachon University Of Medicine And Science
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Kim Ki
Deparment Of Obstetrics & Gynecology College Of Medicine Pusan National University
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