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 EC(50) ≈ 6 μM. This [Ca(2+)](i) response was abolished...
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1826277519407448064 |
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| author | Buckler, K |
| author_facet | Buckler, K |
| author_sort | Buckler, K |
| collection | OXFORD |
| description | 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 EC(50) ≈ 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. |
| first_indexed | 2024-03-06T23:30:07Z |
| format | Journal article |
| id | oxford-uuid:6bbdbbe8-e28d-4347-a171-589ff8ac134f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:30:07Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:6bbdbbe8-e28d-4347-a171-589ff8ac134f2022-03-26T19:06:09ZEffects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K channel activity and mitochondrial function in chemoreceptor cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6bbdbbe8-e28d-4347-a171-589ff8ac134fEnglishSymplectic Elements at Oxford2012Buckler, KIt 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 EC(50) ≈ 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. |
| spellingShingle | Buckler, K Effects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K channel activity and mitochondrial function in chemoreceptor cells. |
| title | Effects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K channel activity and mitochondrial function in chemoreceptor cells. |
| title_full | Effects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K channel activity and mitochondrial function in chemoreceptor cells. |
| title_fullStr | Effects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K channel activity and mitochondrial function in chemoreceptor cells. |
| title_full_unstemmed | Effects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K channel activity and mitochondrial function in chemoreceptor cells. |
| title_short | Effects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K channel activity and mitochondrial function in chemoreceptor cells. |
| title_sort | effects of exogenous hydrogen sulphide on calcium signalling background task k channel activity and mitochondrial function in chemoreceptor cells |
| work_keys_str_mv | AT bucklerk effectsofexogenoushydrogensulphideoncalciumsignallingbackgroundtaskkchannelactivityandmitochondrialfunctioninchemoreceptorcells |