Voltage‐Gated Na⁺ Channel Activity and Connexin Expression in C×43‐Deficient Cardiac Myocytes

Abstract

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.

Null Mutation of Connexin43 Causes Slow Propagation of Ventricular Activation in the Late Stages of Mouse Embryonic Development

“…The observation that the dV/dt max is not reduced in the Cx43 Ϫ/Ϫ embryos suggests that the slow propagation seen at this time point is not a result of a concurrent reduction in excitatory currents. This is consistent with the findings of Johnson et al, 40 who studied sodium currents in Cx43 Ϫ/Ϫ animals at term. However, that study found no increase in the upstroke velocity in isolated myocytes.…”

“…However, that study found no increase in the upstroke velocity in isolated myocytes. 40 The paradoxic increase in the upstroke velocity gives credence to a computational prediction of Rudy and Quan 41 that in the presence of unchanged excitatory currents, the higher input resistance of poorly coupled cells must result in higher upstroke velocities. Note that only RV and not LV conduction velocity was found to be reduced in the Cx43 Ϫ/Ϫ heart at 15.5 dpc.…”

Autocrine Regulation of Myocyte Cx43 Expression by VEGF

“…Aliquots containing 7 g of total protein were analyzed by SDS polyacrylamide gel electrophoresis, and Cx43 signal was quantified as described in detail in previous studies. 6 In all experiments, Cx43 signal in experimental preparations was compared with signal from control cultures (cells incubated in serum-free medium for 1 hour but not subjected to stretch or exposed to VEGF or antibodies), which was normalized to a value of 1.0.…”

Alterations of Phosphorylation State of Connexin 43 during Hypoxia and Reoxygenation Are Associated with Cardiac Function

“…Connexin 37 (Cx37), Cx40, Cx43, Cx45, Cx46, and Cx50 are expressed in mammalian cardiomyocytes (Darrow et al 1995;Saffitz et al 2000;Polontchouk et al 2002). Studies using Cx43-deficient mice have demonstrated that Cx43 is the principal protein for ventricular electrical coupling (Reaume et al 1995;Ya et al 1998;Johnson et al 1999;Gutstein et al 2001).…”