Idiopathic ventricular outflow tract tachycardia

Abstract

Although the pathogenesis of ventricular outflow tract tachycardia has not been fully elucidated, recent findings suggest that defects in cAMP signalling may be involved.

Figure 1

Receptor schema for activation and inactivation of cAMP mediated triggered activity caused by delayed afterdepolarisations. β adrenergic receptor stimulation (β-AR) results in the stimulatory G-protein (G_s) releasing its bound GDP and binding GTP. The active G_αs-GTP complex then dissociates from G_βγ and stimulates adenylyl cyclase (AC), leading to an increase in cAMP and activation of protein kinase A (PKA). This results in an increase of the slow inward calcium current (I_Ca(L)) as well as an increase in calcium release from the sarcoplasmic reticulum (SR), with consequent activation of a transient inward current (I_TI) through the Na⁺-Ca²⁺ exchanger (Na-CaX). Adenosine (ADO), by binding to the adenosine A₁ receptor (A₁R), acts via an inhibitory G-protein G_i. In response to adenosine binding, G_i releases its bound GDP and binds GTP. The active G_αi-GTP complex then dissociates from G_βγ and inhibits adenylyl cyclase. This leads to a decrease in I_Ca(L) and SR calcium release with consequent attenuation of (I_TI). ACh, acetylcholine; ISO, isoproterenol; M₂R, muscarinic cholinergic receptor.