Inward rectification in KATP channels: a pH switch in the pore.
Inward-rectifier potassium channels (Kir channels) stabilize the resting membrane potential and set a threshold for excitation in many types of cell. This function arises from voltage-dependent rectification of these channels due to blockage by intracellular polyamines. In all Kir channels studied t...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
1999
|
| _version_ | 1826266571830460416 |
|---|---|
| author | Baukrowitz, T Tucker, S Schulte, U Benndorf, K Ruppersberg, J Fakler, B |
| author_facet | Baukrowitz, T Tucker, S Schulte, U Benndorf, K Ruppersberg, J Fakler, B |
| author_sort | Baukrowitz, T |
| collection | OXFORD |
| description | Inward-rectifier potassium channels (Kir channels) stabilize the resting membrane potential and set a threshold for excitation in many types of cell. This function arises from voltage-dependent rectification of these channels due to blockage by intracellular polyamines. In all Kir channels studied to date, the voltage-dependence of rectification is either strong or weak. Here we show that in cardiac as well as in cloned KATP channels (Kir6.2 + sulfonylurea receptor) polyamine-mediated rectification is not fixed but changes with intracellular pH in the physiological range: inward-rectification is prominent at basic pH, while at acidic pH rectification is very weak. The pH-dependence of polyamine block is specific for KATP as shown in experiments with other Kir channels. Systematic mutagenesis revealed a titratable C-terminal histidine residue (H216) in Kir6.2 to be the structural determinant, and electrostatic interaction between this residue and polyamines was shown to be the molecular mechanism underlying pH-dependent rectification. This pH-dependent block of KATP channels may represent a novel and direct link between excitation and intracellular pH. |
| first_indexed | 2024-03-06T20:40:59Z |
| format | Journal article |
| id | oxford-uuid:34470e7a-fab7-413e-956c-1ef21cb43268 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:40:59Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:34470e7a-fab7-413e-956c-1ef21cb432682022-03-26T13:25:02ZInward rectification in KATP channels: a pH switch in the pore.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:34470e7a-fab7-413e-956c-1ef21cb43268EnglishSymplectic Elements at Oxford1999Baukrowitz, TTucker, SSchulte, UBenndorf, KRuppersberg, JFakler, BInward-rectifier potassium channels (Kir channels) stabilize the resting membrane potential and set a threshold for excitation in many types of cell. This function arises from voltage-dependent rectification of these channels due to blockage by intracellular polyamines. In all Kir channels studied to date, the voltage-dependence of rectification is either strong or weak. Here we show that in cardiac as well as in cloned KATP channels (Kir6.2 + sulfonylurea receptor) polyamine-mediated rectification is not fixed but changes with intracellular pH in the physiological range: inward-rectification is prominent at basic pH, while at acidic pH rectification is very weak. The pH-dependence of polyamine block is specific for KATP as shown in experiments with other Kir channels. Systematic mutagenesis revealed a titratable C-terminal histidine residue (H216) in Kir6.2 to be the structural determinant, and electrostatic interaction between this residue and polyamines was shown to be the molecular mechanism underlying pH-dependent rectification. This pH-dependent block of KATP channels may represent a novel and direct link between excitation and intracellular pH. |
| spellingShingle | Baukrowitz, T Tucker, S Schulte, U Benndorf, K Ruppersberg, J Fakler, B Inward rectification in KATP channels: a pH switch in the pore. |
| title | Inward rectification in KATP channels: a pH switch in the pore. |
| title_full | Inward rectification in KATP channels: a pH switch in the pore. |
| title_fullStr | Inward rectification in KATP channels: a pH switch in the pore. |
| title_full_unstemmed | Inward rectification in KATP channels: a pH switch in the pore. |
| title_short | Inward rectification in KATP channels: a pH switch in the pore. |
| title_sort | inward rectification in katp channels a ph switch in the pore |
| work_keys_str_mv | AT baukrowitzt inwardrectificationinkatpchannelsaphswitchinthepore AT tuckers inwardrectificationinkatpchannelsaphswitchinthepore AT schulteu inwardrectificationinkatpchannelsaphswitchinthepore AT benndorfk inwardrectificationinkatpchannelsaphswitchinthepore AT ruppersbergj inwardrectificationinkatpchannelsaphswitchinthepore AT faklerb inwardrectificationinkatpchannelsaphswitchinthepore |