PMID- 7576597
OWN - NLM
STAT- MEDLINE
DCOM- 19951205
LR  - 20191210
IS  - 0958-0670 (Print)
IS  - 0958-0670 (Linking)
VI  - 80
IP  - 4
DP  - 1995 Jul
TI  - Muscarinic suppression of Ca2+ current in smooth muscle cells of the guinea-pig 
      urinary bladder.
PG  - 575-87
AB  - The suppressive action of carbachol (CCh) on the Ca2+ current (ICa) in smooth 
      muscle cells of the guinea-pig urinary bladder was investigated using the 
      whole-cell patch clamp technique. Bath application of 10 microM CCh reduced the 
      amplitude of ICa by 92 +/- 3.8% (n = 9). Adding 1 microM atropine to the bath 
      completely blocked the action of CCh, indicating that the suppressive action of 
      CCh on ICa is mediated by the activation of muscarinic receptors. Intracellular 
      perfusion of the non-hydrolysable GTP analogue, guanosine 
      5'-O-(3-thiotriphosphate) (GTP gamma S; 200 microM) mimicked the effects of CCh. 
      Sustained suppression of ICa was observed when GTP gamma S was present in the 
      cytoplasm. Intracellular perfusion of inositol 1,4,5-trisphosphate (InsP 3; 20 
      microM) also suppressed ICa; its effect was not sustained but transient. The 
      protein kinase C activator, phorbol 12,13-dibutyrate (PDBu), however, could not 
      mimic the effects of CCh on ICa. When intracellular Ca2+ was strongly buffered by 
      the Ca2+ chelator EGTA (20 mM) in the patch pipette, the sustained suppression of 
      ICa was abolished. Inclusion of 3 mg/ml heparin, a blocker of InsP3-induced Ca2+ 
      release, in the patch pipette reduced the degree of sustained ICa suppression by 
      43.2 +/- 1.9% (n = 7). Adding thapsigargin (TG), a sarcoplasmic reticulum 
      Ca2+-ATPase inhibitor, to a wash solution reduced the recovery of ICa by about 
      50%, suggesting that approximately half of the ICa suppression induced by CCh is 
      due to Ca2+ release from TG-sensitive internal Ca2+ stores. From these results it 
      appears that CCh suppresses ICa via two independent mechanisms: (1) 
      Ca(2+)-mediated inactivation of the Ca2+ channel, which is caused by Ca2+ release 
      from InsP3- and TG-sensitive internal stores, and (2) a GTP-binding 
      protein-mediated mechanism, which requires intracellular Ca2+.
FAU - Yoshino, M
AU  - Yoshino M
AD  - Department of Physiology, Sapporo Medical University, Japan.
FAU - Yabu, H
AU  - Yabu H
LA  - eng
PT  - Journal Article
PL  - England
TA  - Exp Physiol
JT  - Experimental physiology
JID - 9002940
RN  - 0 (Terpenes)
RN  - 67526-95-8 (Thapsigargin)
RN  - 7T101UWZ5W (Muscarine)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - 8Y164V895Y (Carbachol)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*physiology
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Carbachol/pharmacology
MH  - Electric Conductivity
MH  - GTP-Binding Proteins/physiology
MH  - Guinea Pigs
MH  - Inositol 1,4,5-Trisphosphate/physiology
MH  - Male
MH  - Muscarine/*metabolism
MH  - Muscle, Smooth/cytology/*physiology
MH  - Protein Kinase C/physiology
MH  - Terpenes/pharmacology
MH  - Thapsigargin
MH  - Urinary Bladder/cytology/*physiology
EDAT- 1995/07/01 00:00
MHDA- 1995/07/01 00:01
CRDT- 1995/07/01 00:00
PHST- 1995/07/01 00:00 [pubmed]
PHST- 1995/07/01 00:01 [medline]
PHST- 1995/07/01 00:00 [entrez]
AID - 10.1113/expphysiol.1995.sp003868 [doi]
PST - ppublish
SO  - Exp Physiol. 1995 Jul;80(4):575-87. doi: 10.1113/expphysiol.1995.sp003868.