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 H2S mediates oxygen sensing in chemoreceptors; this study investigates the mechanisms by which H 2S excites carotid body type 1 cells. H2S caused a rapid reversible increase in intracellular calcium with EC50≈6 μM. This [Ca2+]i response was abolished in Ca-free T...
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| Formatua: | Journal article |
| Hizkuntza: | English |
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2012
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| _version_ | 1826273886721802240 |
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| author | Buckler, K |
| author_facet | Buckler, K |
| author_sort | Buckler, K |
| collection | OXFORD |
| description | It has been proposed that endogenous H2S mediates oxygen sensing in chemoreceptors; this study investigates the mechanisms by which H 2S excites carotid body type 1 cells. H2S caused a rapid reversible increase in intracellular calcium with EC50≈6 μM. This [Ca2+]i response was abolished in Ca-free Tyrode. In perforated patch current clamp recordings, H2S 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 H2S-induced rise in [Ca2+]i. H2S inhibited background K+current in whole cell perforated patch and reduced background K+ channel activity in cell-attached patch recordings. It is concluded that H2S excites type 1 cells through the inhibition of background (TASK) potassium channels leading to membrane depolarisation and voltage-gated Ca2+ entry. These effects mimic those of hypoxia. H2S 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 H2S and prevented H2S exerting any further influence over channel activity. These data indicate that the effects of H2S on background K channels are a consequence of inhibition of oxidative phosphorylation. Whilst this does not preclude a role for endogenous H2S in oxygen sensing via the inhibition of cytochrome oxidase, the levels of H2S required raise questions as to the viability of such a mechanism. © Springer-Verlag 2012. |
| first_indexed | 2024-03-06T22:35:03Z |
| format | Journal article |
| id | oxford-uuid:59993c18-039e-43c8-a07f-59d53a8e795f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:35:03Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:59993c18-039e-43c8-a07f-59d53a8e795f2022-03-26T17:10:42ZEffects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K channel activity and mitochondrial function in chemoreceptor cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:59993c18-039e-43c8-a07f-59d53a8e795fEnglishSymplectic Elements at Oxford2012Buckler, KIt has been proposed that endogenous H2S mediates oxygen sensing in chemoreceptors; this study investigates the mechanisms by which H 2S excites carotid body type 1 cells. H2S caused a rapid reversible increase in intracellular calcium with EC50≈6 μM. This [Ca2+]i response was abolished in Ca-free Tyrode. In perforated patch current clamp recordings, H2S 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 H2S-induced rise in [Ca2+]i. H2S inhibited background K+current in whole cell perforated patch and reduced background K+ channel activity in cell-attached patch recordings. It is concluded that H2S excites type 1 cells through the inhibition of background (TASK) potassium channels leading to membrane depolarisation and voltage-gated Ca2+ entry. These effects mimic those of hypoxia. H2S 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 H2S and prevented H2S exerting any further influence over channel activity. These data indicate that the effects of H2S on background K channels are a consequence of inhibition of oxidative phosphorylation. Whilst this does not preclude a role for endogenous H2S in oxygen sensing via the inhibition of cytochrome oxidase, the levels of H2S required raise questions as to the viability of such a mechanism. © Springer-Verlag 2012. |
| 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 |