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Figure 4 Hypothetic pathophysiologic mechanism of tachycardia in patients with idiopathic RVO-VT. Reduced reuptake (UP) of norepinephrine (NE) into the nerve terminal or increased release (RE) into the synaptic cleft leads to an increase in local norepinephrine concentration in the synaptic cleft and stimulation of postsynaptic beta-adrenoceptors (ß-AR). In turn this leads to increased cyclic adenosine monophosphate (cAMP) through activation of the stimulatory G protein (GS) and adenylyl cyclase (AC). The increase in cAMP will produce a rise in intracellular Ca2+ levels by activation of protein kinase A (PKA) and will eventually trigger ventricular tachycardia. That this occurs despite beta-adrenoceptor downregulation suggests that norepinephrine is still capable of significantly increasing intracellular cAMP concentration, probably due to changes in the beta-adrenoceptor–G-protein–adenylyl cyclase pathway.
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