The extracellular loop of the auxiliary ß1-subunit is involved in the regulation of BKCa channel mechanosensitivity.
Am J Physiol Cell Physiol
; 315(4): C485-C493, 2018 10 01.
Article
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| MEDLINE
| ID: mdl-29924635
ABSTRACT
The large conductance Ca2+-activated potassium (BKCa) channel is activated by stretch. The stress-regulated exon (STREX) in α-subunits is known to affect the mechanosensitivity of BKCa channels. However, in human colonic smooth muscle cells (HCoSMCs), we found that the α-subunits without STREX (ZERO-BK) and ß1-subunits could be detected yet the cells were mechanosensitive. Whether the ß1-subunit is involved in the regulation of BKCa mechanosensitivity is unclear. In the present study, ZERO-BK and ß1-subunits were individually expressed or coexpressed in HEK293 cells and cell-attached patch-clamp techniques were used to measure BKCa currents defining mechanosensitivity. Single-channel patch-clamp recordings from HEK293 cells cotransfected with ZERO-BK and ß1-subunits showed stretch sensitivity, but there was no mechanosensitivity in HEK293 cells transfected only with ZERO-BK. We also showed that expression of the ß1-subunit could increase mechanosensitivity of the STREX-type α-subunits (STREX-BK). To identify the domain in ß1-subunits responsible for affecting stretch sensitivity, we expressed ß1- LoopDel (chimeric ß1-subunits without the extracellular loop) or ß1- C TermDel (chimeric ß1-subunits without COOH terminus) with ZERO-BK in HEK293 cells. The data showed that deletion of the extracellular loop but not the COOH terminus of ß1-subunits virtually abolished the mechanosensitivity. These results suggest that the extracellular loop of the ß1-subunit is involved in the regulation of BKCa channel mechanosensitivity and that role is independent of STREX.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Subunidades de Proteína
/
Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Asunto de la revista:
FISIOLOGIA
Año:
2018
Tipo del documento:
Article