Atrial fibrillation-associated connexin40 mutants make hemichannels and synergistically form gap junction channels with novel properties.
Mutations of Cx40 (GJA5) have been identified in people with lone chronic atrial fibrillation including G38D and M163V which were found in the same patient. We used dual whole cell patch clamp procedures to examine the transjunctional voltage (Vj) gating and channel conductance properties of these two rare mutants. Each mutant exhibited slight alterations of Vj gating properties and increased the gap junction channel conductance (γj) by 20-30 pS. While co-expression of the two mutations had similar effects on Vj gating, it synergistically increased γj by 50%. Unlike WTCx40 or M163V, G38D induced activity of a dominant 271 pS hemichannel.
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Dakshesh
D
Patel
Department of Pediatrics, University of Chicago, Chicago, IL 60637, United States.
Joanna
J
Gemel
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Qin
Q
Xu
Department of Pediatrics, University of Chicago, Chicago, IL 60637, United States.
Adria R
AR
Simon
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Xianming
X
Lin
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Arvydas
A
Matiukas
Department of Pediatrics, University of Chicago, Chicago, IL 60637, United States.
Eric C
EC
Beyer
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States; Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, United States. Electronic address: veenstrr@upstate.edu.
Richard D
RD
Veenstra
D000200:Action Potentials; D001281:Atrial Fibrillation / Q000235:genetics; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008564:Membrane Potentials; D009154:Mutation; D000097003:Gap Junction alpha-5 Protein
D017630:Connexins; D000097003:Gap Junction alpha-5 Protein
Atrial fibrillation; Channel conductance; Connexin40; Gap junctions; Hemichannels