Nonselective cation channels activated by the stimulation of muscarinic receptors in mammalian gastric smooth muscle

Insuk So, Ki Whan Kim

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 (ICCh), especially the steady-state I-V relationship of ICCh 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 Ca2+ through changing both the open probability and unitary conductance. Through the NSCC, Ca2+ can move into the cell from extracellular solution as well as Na+. Calculated fractional Ca2+ current of ICCh (fCa) was around 1% at the 2 mM [Ca2+]o and at the 4 mM [Ca2+]o, fCa was 2.3%. Quinidine blocked ICCh potently in a reversible manner; IC50 was 0.25 mM. There were two kinds of ICCh modulations through Ca2+-dependent pathways in guinea-pig gastric smooth muscle cells; 1) Facilitation of ICCh via Ca2+/CaM-dependent MLCK pathway, 2) Desensitization of ICCh via Ca2+-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 mTRPC5 as a candidate for the NSCC activated by muscarinic stimulation in mouse stomach.

Original languageEnglish
Pages (from-to)231-247
Number of pages17
JournalJournal of Smooth Muscle Research
Volume32
Issue number3
StatePublished - 1 Dec 1996

Fingerprint

Muscarinic Receptors
Smooth Muscle
Cations
Stomach
Guinea Pigs
Smooth Muscle Myocytes
Pyloric Antrum
Monovalent Cations
Polymerase Chain Reaction
Quinidine
Pertussis Toxin
Divalent Cations
Cholinergic Agents
Inhibitory Concentration 50
Pharmacology
Messenger RNA
Proteins

Keywords

  • Fractional Ca current of I
  • Modulation of I
  • Nonselective cation channel
  • Quinidine
  • TRPC

Cite this

@article{eca6c69d81c746bcbe92c5631447b3ed,
title = "Nonselective cation channels activated by the stimulation of muscarinic receptors in mammalian gastric smooth muscle",
abstract = "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 (ICCh), especially the steady-state I-V relationship of ICCh 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 Ca2+ through changing both the open probability and unitary conductance. Through the NSCC, Ca2+ can move into the cell from extracellular solution as well as Na+. Calculated fractional Ca2+ current of ICCh (fCa) was around 1{\%} at the 2 mM [Ca2+]o and at the 4 mM [Ca2+]o, fCa was 2.3{\%}. Quinidine blocked ICCh potently in a reversible manner; IC50 was 0.25 mM. There were two kinds of ICCh modulations through Ca2+-dependent pathways in guinea-pig gastric smooth muscle cells; 1) Facilitation of ICCh via Ca2+/CaM-dependent MLCK pathway, 2) Desensitization of ICCh via Ca2+-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 mTRPC5 as a candidate for the NSCC activated by muscarinic stimulation in mouse stomach.",
keywords = "Fractional Ca current of I, Modulation of I, Nonselective cation channel, Quinidine, TRPC",
author = "Insuk So and Kim, {Ki Whan}",
year = "1996",
month = "12",
day = "1",
language = "English",
volume = "32",
pages = "231--247",
journal = "Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi",
issn = "0916-8737",
publisher = "Japan Society of Smooth Muscle Research",
number = "3",

}

Nonselective cation channels activated by the stimulation of muscarinic receptors in mammalian gastric smooth muscle. / So, Insuk; Kim, Ki Whan.

In: Journal of Smooth Muscle Research, Vol. 32, No. 3, 01.12.1996, p. 231-247.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Nonselective cation channels activated by the stimulation of muscarinic receptors in mammalian gastric smooth muscle

AU - So, Insuk

AU - Kim, Ki Whan

PY - 1996/12/1

Y1 - 1996/12/1

N2 - 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 (ICCh), especially the steady-state I-V relationship of ICCh 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 Ca2+ through changing both the open probability and unitary conductance. Through the NSCC, Ca2+ can move into the cell from extracellular solution as well as Na+. Calculated fractional Ca2+ current of ICCh (fCa) was around 1% at the 2 mM [Ca2+]o and at the 4 mM [Ca2+]o, fCa was 2.3%. Quinidine blocked ICCh potently in a reversible manner; IC50 was 0.25 mM. There were two kinds of ICCh modulations through Ca2+-dependent pathways in guinea-pig gastric smooth muscle cells; 1) Facilitation of ICCh via Ca2+/CaM-dependent MLCK pathway, 2) Desensitization of ICCh via Ca2+-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 mTRPC5 as a candidate for the NSCC activated by muscarinic stimulation in mouse stomach.

AB - 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 (ICCh), especially the steady-state I-V relationship of ICCh 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 Ca2+ through changing both the open probability and unitary conductance. Through the NSCC, Ca2+ can move into the cell from extracellular solution as well as Na+. Calculated fractional Ca2+ current of ICCh (fCa) was around 1% at the 2 mM [Ca2+]o and at the 4 mM [Ca2+]o, fCa was 2.3%. Quinidine blocked ICCh potently in a reversible manner; IC50 was 0.25 mM. There were two kinds of ICCh modulations through Ca2+-dependent pathways in guinea-pig gastric smooth muscle cells; 1) Facilitation of ICCh via Ca2+/CaM-dependent MLCK pathway, 2) Desensitization of ICCh via Ca2+-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 mTRPC5 as a candidate for the NSCC activated by muscarinic stimulation in mouse stomach.

KW - Fractional Ca current of I

KW - Modulation of I

KW - Nonselective cation channel

KW - Quinidine

KW - TRPC

UR - http://www.scopus.com/inward/record.url?scp=84884565402&partnerID=8YFLogxK

M3 - Article

VL - 32

SP - 231

EP - 247

JO - Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi

JF - Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi

SN - 0916-8737

IS - 3

ER -