G-Protein β Subunit Mutations in Sinus Node Dysfunction
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
The sinoatrial node (SAN) is the normal pacemaker of the mammalian heart and generates the electric impulse for the regular, rhythmic contraction of the heart. Pacemaker activity of SAN cells is based on the diastolic depolarization phase of action potential, during which they depolarize spontaneously toward the action potential threshold. Diastolic depolarization is achieved by a miniscule net inward (depolarizing) current across the cell membrane. This net inward current is because of a complex system of 2 clocks. The first, named the Ca2+ clock, is the result of tightly regulated sarcoplasmic reticulum Ca2+ cycling working together with the electrogenic Na+–Ca2+ exchanger.1 The second, named the membrane clock, is caused by sarcolemmal ion currents.2 The diastolic depolarization rate, and thus the intrinsic cycle length of SAN cells (or pacing), is modulated through the opposing influences of adrenergic and muscarinic stimulation via G-protein–coupled receptor signaling.3 Adrenergic stimulation accelerates pacemaker activity by increasing the speed of the Ca2+ clock1 and by increasing components of the membrane clock such as the inwardly directed hyperpolarization-activated pacemaker current (funny current, If) and the L-type Ca2+ current, ICa,L.2 On the contrary, acetylcholine-mediated stimulation of muscarinic receptors decelerates pacemaker activity by decreasing the speed of the Ca2+ clock1 and by activating among others the outwardly directed acetylcholine-sensitive K+ current IK,ACh.3,4
Article, see p e33
Impaired pacemaker activity, termed sinus node dysfunction (SND) or sick sinus syndrome, has been defined as the intrinsic inadequacy of the SAN to perform its pacemaker function because of a disorder of automaticity and inability to transmit its impulse to the rest of the atrium.5 In the young, SND is rare and when present it typically has a familial presentation. …