G protein modulation of voltage-sensitive muscarinic receptor signalling in mouse pancreatic acinar cells

Boon Hooi Ong, Atsushi Ohsaga, Kozo Sato, Takako Oshiro, Kunio Shirato, Yoshio Maruyama

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Submaximal stimulation of mouse pancreatic acinar cells by acetylcholine (ACh) generates periodic Ca2+ responses sensitive to the membrane potential. Monitoring the muscarinic Ca2+ responses using patch-clamp whole-cell current recordings, we examined the mechanism of guanine nucleotide-binding protein (G protein)-receptor interaction in terms of the membrane potential. The lowest ACh concentration able to elicit consistent repetitive spikes was 50 nM, in the presence of which hyperpolarization increased and depolarization decreased the spike frequency. The saturating concentration was 10 μM, this induced a sustained response insensitive to voltage. Internal guanosine 5′-tri- and diphosphates (GTP, GDP) depressed and potentiated the voltage sensitivity, respectively, but not for the response to a saturating ACh concentration (10 μM). Internal guanosine 5′-O-(3-thiotriphosphate) (GTPγS) abolished the voltage sensitivity. The results indicate that the ACh-induced Ca2+ response is sensitive to the membrane potential and that a close linkage exists between voltage sensitivity and the G protein association/dissociation cycle in the muscarinic receptor.

Original languageEnglish
Pages (from-to)604-610
Number of pages7
JournalPflugers Archiv European Journal of Physiology
Volume441
Issue number5
DOIs
Publication statusPublished - 2001

Keywords

  • Ca responses
  • G protein modulation
  • Muscarinic ACh receptors
  • Pancreatic acinar cells
  • Voltage sensitivity

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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