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 H 2 S mediates oxygen sensing in chemoreceptors; this study investigates the mechanisms by which H 2 S excites carotid body type 1 cells. H 2 S caused a rapid reversible increase in intracellular calcium with EC5 0 ≈6 μM. This [Ca 2+ ] i response was abolished in Ca-free Tyrode. In perforated patch current clamp recordings, H 2 S depolarised type 1 cells from -59 to -35 mV; this was accompanied by a robust increase in [Ca 2+ ] i . Voltage clamping at the resting membrane potential abolished the H 2 S-induced rise in [Ca 2+ ] i . H 2 S inhibited background K + current in whole cell perforated patch and reduced background K + channel activity in cell-attached patch recordings. It is concluded that H 2 S excites type 1 cells through the inhibition of background (TASK) potassium channels leading to membrane depolarisation and voltage-gated Ca 2+ entry. These effects mimic those of hypoxia. H 2 S 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 H 2 S and prevented H 2 S exerting any further influence over channel activity. These data indicate that the effects of H 2 S on background K channels are a consequence of inhibition of oxidative phosphorylation. Whilst this does not preclude a role for endogenous H 2 S in oxygen sensing via the inhibition of cytochrome oxidase, the levels of H 2 S required raise questions as to the viability of such a mechanism. © Springer-Verlag 2012.