PMID- 10362599
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20231213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 276
IP  - 6
DP  - 1999 Jun
TI  - Is the chemical gate of connexins voltage sensitive? Behavior of Cx32 wild-type 
      and mutant channels.
PG  - C1361-73
LID - 10.1152/ajpcell.1999.276.6.C1361 [doi]
AB  - Connexin channels are gated by transjunctional voltage (Vj) or CO2 via distinct 
      mechanisms. The cytoplasmic loop (CL) and arginines of a COOH-terminal domain 
      (CT1) of connexin32 (Cx32) were shown to determine CO2 sensitivity, and a gating 
      mechanism involving CL-CT1 association-dissociation was proposed. This study 
      reports that Cx32 mutants, tandem, 5R/E, and 5R/N, designed to weaken CL-CT1 
      interactions, display atypical Vj and CO2 sensitivities when tested 
      heterotypically with Cx32 wild-type channels in Xenopus oocytes. In tandems, two 
      Cx32 monomers are linked NH2-to-COOH terminus. In 5R/E and 5R/N mutants, 
      glutamates or asparagines replace CT1 arginines. On the basis of the intriguing 
      sensitivity of the mutant-32 channel to Vj polarity, the existence of a "slow 
      gate" distinct from the conventional Vj gate is proposed. To a lesser extent the 
      slow gate manifests itself also in homotypic Cx32 channels. Mutant-32 channels 
      are more CO2 sensitive than homotypic Cx32 channels, and CO2-induced chemical 
      gating is reversed with relative depolarization of the mutant oocyte, suggesting 
      Vj sensitivity of chemical gating. A hypothetical pore-plugging model involving 
      an acidic cytosolic protein (possibly calmodulin) is discussed.
FAU - Peracchia, C
AU  - Peracchia C
AD  - Department of Pharmacology and Physiology, School of Medicine and Dentistry, 
      University of Rochester, Rochester, New York 14642-8711, USA. 
      cpera@pharmacol.rochester.edu
FAU - Wang, X G
AU  - Wang XG
FAU - Peracchia, L L
AU  - Peracchia LL
LA  - eng
GR  - GM-20113/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Connexins)
RN  - 0 (Ion Channels)
RN  - 142M471B3J (Carbon Dioxide)
SB  - IM
MH  - Animals
MH  - Carbon Dioxide/physiology
MH  - Connexins/*chemistry/*metabolism/*physiology
MH  - Electric Conductivity
MH  - Electrochemistry
MH  - Electrophysiology
MH  - Female
MH  - Gap Junctions/physiology
MH  - Homeostasis/physiology
MH  - Ion Channel Gating/*physiology
MH  - Ion Channels/*genetics/*metabolism
MH  - Mutation/*physiology
MH  - Reference Values
MH  - Xenopus laevis
MH  - Gap Junction beta-1 Protein
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1152/ajpcell.1999.276.6.C1361 [doi]
PST - ppublish
SO  - Am J Physiol. 1999 Jun;276(6):C1361-73. doi: 10.1152/ajpcell.1999.276.6.C1361.