Effects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K channel activity and mitochondrial function in chemoreceptor cells.

It has been proposed that endogenous HS mediates oxygen sensing in chemoreceptors; this study investigates the mechanisms by which HS excites carotid body type 1 cells. HS caused a rapid reversible increase in intracellular calcium with EC ≈ 6 μM. This [Ca] response was abolished in Ca-free Tyrode. In perforated patch current clamp recordings, HS depolarised type 1 cells from −59 to −35 mV; this was accompanied by a robust increase in [Ca]. Voltage clamping at the resting membrane potential abolished the HS-induced rise in [Ca]. HS inhibited background K current in whole cell perforated patch and reduced background K channel activity in cell-attached patch recordings. It is concluded that HS excites type 1 cells through the inhibition of background (TASK) potassium channels leading to membrane depolarisation and voltage-gated Ca entry. These effects mimic those of hypoxia. HS also inhibited mitochondrial function over a similar concentration range as assessed by NADH autofluorescence and measurement of intracellular magnesium (an index of decline in MgATP). Cyanide inhibited background K channels to a similar extent to HS and prevented HS exerting any further influence over channel activity. These data indicate that the effects of HS on background K channels are a consequence of inhibition of oxidative phosphorylation. Whilst this does not preclude a role for endogenous HS in oxygen sensing via the inhibition of cytochrome oxidase, the levels of HS required raise questions as to the viability of such a mechanism. [ABSTRACT FROM AUTHOR]