Voltage-gated Na+ channel activity and connexin expression in Cx43-deficient cardiac myocytes.
BACKGROUND
Dynamic interplay between active and passive electrical properties of cardiac myocytes is based on interrelationships between various channels responsible for depolarizing and repolarizing ionic currents and intercellular conductances. Mice with targeted disruption of the connexin43 (Cx43) gene have hearts completely devoid of Cx43, the principal gap junctional protein expressed in mammalian hearts.


RESULTS
To determine whether cardiac myocytes that develop in an abnormal environment of reduced intercellular coupling have altered active membrane properties, we studied whole cell action potentials, Na+ channel currents, and Na+ channel expression and distribution via immunoblotting and confocal immunofluorescence in neonatal ventricular myocytes isolated from Cx43 wild-type, heterozygous, and homozygous null hearts. Action potential morphology, peak Na+ current, activation and inactivation kinetics, and Na+ channel protein expression and distribution were not different among myocytes isolated from wild-type, heterozygous, or null hearts. Active membrane properties and Na+ channel activity were completely normal in Cx43-deficient myocytes isolated from hearts that have been shown to exhibit markedly reduced Cx43 expression, gap junction number, and epicardial conduction delay.


CONCLUSIONS
Despite a genetic inability to produce Cx43 and a developmental history that culminates in marked gross cardiac morphologic abnormalities, premature death, and myocardial inexcitability ex vivo, cardiac Na+ channel distribution and function appear to be normal in Cx43 null hearts. Although intimate structural and functional interrelationships have been described between ion channels and gap junction channels, expression and function of Na+ channels is not affected by the absence of Cx43.
Johnson
C M
CM
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Green
K G
KG
Kanter
E M
EM
Bou-Abboud
E
E
Saffitz
J E
JE
Yamada
K A
KA
D000818:Animals; D002478:Cells, Cultured; D018031:Connexin 43 / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009206:Myocardium / Q000166:cytology; D015222:Sodium Channels / Q000502:physiology* / Q000648:ultrastructure
D018031:Connexin 43; D015222:Sodium Channels