Angiotensin II mobilizes intracellular calcium and activates pannexin-1 channels in rat carotid body type II cells via AT1 receptors

摘要: Key points A locally generating, angiotensin II (ANG II) system is present in the rat carotid body (CB) and up-regulation of this occurs certain pathophysiological situations, enhancing sympathetic activity. Here, we show that, similar to chemoreceptor type I cells, glial-like type II cells also express functional AT1Rs, stimulation which causes release Ca2+ from intracellular stores. ANG II–AT1R signalling activates an inward current carried by pannexin-1 (Panx-1) channels are known act as conduits for ATP, a key CB excitatory neurotransmitter. Combined effects ANG II Panx-1 currents via P2Y2 receptors, were synergistic; chelating with BAPTA prevented activation. We propose that function involves dual actions at both II cells. Abstract A local angiotensin-generating increased contributes enhanced excitation chronic heart failure (CHF) after or intermittent hypoxia. have thus far been attributed solely AT1 receptors (AT1Rs) on type I cells. Here, dissociated cultures, stimulates identified P2Y2-receptor-induced elevation (Δ[Ca2+]i). induced dose-dependent (EC50 ∼8 nm), robust Δ[Ca2+]i was reversibly abolished AT1R blocker losartan (1 μm). The ANG II-induced persisted Ca2+-free medium but sensitive store depletion cyclopiazonic acid Similar receptor agonists, (20–1000 nm) activated carbenoxolone (5 μm). This arose variable delay inhibited losartan. Repeated application often led run-down, attributable desensitization. When applied same cell combined ATP synergistic. Current either ligand BAPTA-AM (1 μm), suggesting contributed channel activation. Because open neurotransmitter, it plausible paracrine excitability, especially conditions such CHF sleep apnoea.