β-Adrenergic modulation of myocardial conduction velocity: Connexins vs. sodium current

Sympathetic modulation of electrical activation in normal and infarcted myocardium: implications for arrhythmogenesis

“…On short time scales, ␤-adrenergic stimulation was shown in single cell experiments to increase the sodium current by recruiting sodium channels to the membrane (29). GJs, which can be regulated via a variety of mechanisms, represent a dynamic target of ␤-adrenergic receptor activation (7). This can occur via accumulation of GJs at the intercalated disks, increased GJ expression, and increased permeability or conductance (17), although controversy exists over this latter mechanism (43), occurring via cyclic AMP (cAMP)-protein kinase A (PKA)-mediated phosphorylation of Cx43.…”

“…This can occur via accumulation of GJs at the intercalated disks, increased GJ expression, and increased permeability or conductance (17), although controversy exists over this latter mechanism (43), occurring via cyclic AMP (cAMP)-protein kinase A (PKA)-mediated phosphorylation of Cx43. There is substantial evidence from in vitro preparations that GJ function can be modulated by ␤-adrenergic receptor (BAR) activation on short and long times scales (7). Whether the velocity of muscle-to-muscle propagation directly under the influence of cardiac sympathetic nerves is increased and what are the mechanisms underlying such increases remain unknown.…”

Acute restraint stress provokes sudden cardiac death in normotensive rats and enhances susceptibility to arrhythmogenic effects of adrenaline in spontaneously hypertensive rats

“…Treatment of neonatal rat cardiac myocytes with isoproterenol over 24 h increased Cx43 expression [52]. However, b-adrenoreceptor-mediated changes in gap junction conductance are difficult to assess [47]. The present study showed that ARS induced sudden cardiac and myocardial sympathovagal balance shifts, with sympathetic hyperactivity accompanied by gap junction Cx43 channel remodeling (up-regulation of the Cx43 mRNA expression).…”

“…A sympathovagal balance shift with sympathetic overactivation induced by stressful events has been indicated as the underlying cause of cardiac complications leading to sudden death [1,46]. The activity of the cardiac autonomic nervous system alters heart rate, force and time course of contraction [47]. Sympathetic nerves release noradrenaline that binds predominately to b-adrenoreceptors on ventricular myocytes in order to cause an increase in the force of contraction and speed of relaxation.…”

“…In the present study, Cx43 mRNA expression was used to assess the gap junction remod- eling. Whole heart studies report variable effects of sympathetic nervous system stimulation on ventricular conduction velocity (reviewed by Campbell) [47]. Treatment of neonatal rat cardiac myocytes with isoproterenol over 24 h increased Cx43 expression [52].…”