TY - JOUR
T1 - G protein modulation of voltage-sensitive muscarinic receptor signalling in mouse pancreatic acinar cells
AU - Ong, Boon Hooi
AU - Ohsaga, Atsushi
AU - Sato, Kozo
AU - Oshiro, Takako
AU - Shirato, Kunio
AU - Maruyama, Yoshio
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Ca responses
KW - G protein modulation
KW - Muscarinic ACh receptors
KW - Pancreatic acinar cells
KW - Voltage sensitivity
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U2 - 10.1007/s004240000459
DO - 10.1007/s004240000459
M3 - Article
C2 - 11294241
AN - SCOPUS:0035111970
VL - 441
SP - 604
EP - 610
JO - Pflügers Archiv - European Journal of Physiology
JF - Pflügers Archiv - European Journal of Physiology
SN - 0031-6768
IS - 5
ER -