Matches in SemOpenAlex for { <https://semopenalex.org/work/W4319915619> ?p ?o ?g. }
Showing items 1 to 84 of
84
with 100 items per page.
- W4319915619 endingPage "458a" @default.
- W4319915619 startingPage "458a" @default.
- W4319915619 abstract "The TMEM16A chloride channel represents a fundamental depolarising mechanism in arterial smooth muscle cells (SMCs) and cerebral contractile pericytes. The channel is a proposed target for diseases of impaired vascular tone including stroke, vascular dementia and hypertension; however, the mechanisms of modulation of the channel by synthetic inhibitors and activators are incompletely understood. Here, we provide a functional characterization of a recently disclosed positive allosteric modulator (PAM) of the TMEM16A channel. In the presence of sub-maximal (300 nM) intracellular free Ca2+ concentration [Ca2+]i, PAM activated the heterologously expressed TMEM16A channels at positive and negative potentials (EC50≈4 nM), while being almost ineffective on the closely related TMEM16B channel. PAM did not activate the TMEM16A currents in either the absence of intracellular Ca2+ or in the presence of saturating [Ca2+]i (12 μM). Mutant TMEM16A channels with the intracellular gate constitutively open were much less sensitive to PAM, suggesting that PAM may act as a modifier of TMEM16A channel gating. Consistent with the effects observed in heterologously expressed TMEM16A channels, PAM activated endogenous TMEM16A currents in isolated rat aortic SMCs, promoted contraction of isolated aortic rings and enhanced capillary (pericyte) constriction evoked by endothelin-1 or oxygen-glucose deprivation (OGD) to stimulate cerebral ischemia. Conversely, inhibiting TMEM16A pharmacologically facilitated arterial and pericyte relaxation, and protected against OGD-mediated pericyte cell death. In summary, this work (i) enhances our understanding of fundamental mechanisms of biophysical modulation of the TMEM16A channel and (ii) supports the view that TMEM16A is a key determinant of SMCs and pericytes tone." @default.
- W4319915619 created "2023-02-11" @default.
- W4319915619 creator A5000032532 @default.
- W4319915619 creator A5005303940 @default.
- W4319915619 creator A5026280950 @default.
- W4319915619 creator A5037876897 @default.
- W4319915619 creator A5039905592 @default.
- W4319915619 creator A5041199739 @default.
- W4319915619 creator A5048872737 @default.
- W4319915619 creator A5078895245 @default.
- W4319915619 creator A5081643671 @default.
- W4319915619 creator A5085948404 @default.
- W4319915619 date "2023-02-01" @default.
- W4319915619 modified "2023-09-25" @default.
- W4319915619 title "New insights into the molecular basis of allosteric activation of the TMEM16A channel and consequences for the control of vascular tone" @default.
- W4319915619 doi "https://doi.org/10.1016/j.bpj.2022.11.2463" @default.
- W4319915619 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36784350" @default.
- W4319915619 hasPublicationYear "2023" @default.
- W4319915619 type Work @default.
- W4319915619 citedByCount "0" @default.
- W4319915619 crossrefType "journal-article" @default.
- W4319915619 hasAuthorship W4319915619A5000032532 @default.
- W4319915619 hasAuthorship W4319915619A5005303940 @default.
- W4319915619 hasAuthorship W4319915619A5026280950 @default.
- W4319915619 hasAuthorship W4319915619A5037876897 @default.
- W4319915619 hasAuthorship W4319915619A5039905592 @default.
- W4319915619 hasAuthorship W4319915619A5041199739 @default.
- W4319915619 hasAuthorship W4319915619A5048872737 @default.
- W4319915619 hasAuthorship W4319915619A5078895245 @default.
- W4319915619 hasAuthorship W4319915619A5081643671 @default.
- W4319915619 hasAuthorship W4319915619A5085948404 @default.
- W4319915619 hasConcept C123012128 @default.
- W4319915619 hasConcept C12554922 @default.
- W4319915619 hasConcept C134018914 @default.
- W4319915619 hasConcept C166342909 @default.
- W4319915619 hasConcept C169760540 @default.
- W4319915619 hasConcept C181199279 @default.
- W4319915619 hasConcept C185592680 @default.
- W4319915619 hasConcept C194544171 @default.
- W4319915619 hasConcept C202751555 @default.
- W4319915619 hasConcept C2779395532 @default.
- W4319915619 hasConcept C2780427682 @default.
- W4319915619 hasConcept C2992686903 @default.
- W4319915619 hasConcept C55493867 @default.
- W4319915619 hasConcept C79879829 @default.
- W4319915619 hasConcept C86803240 @default.
- W4319915619 hasConcept C95444343 @default.
- W4319915619 hasConceptScore W4319915619C123012128 @default.
- W4319915619 hasConceptScore W4319915619C12554922 @default.
- W4319915619 hasConceptScore W4319915619C134018914 @default.
- W4319915619 hasConceptScore W4319915619C166342909 @default.
- W4319915619 hasConceptScore W4319915619C169760540 @default.
- W4319915619 hasConceptScore W4319915619C181199279 @default.
- W4319915619 hasConceptScore W4319915619C185592680 @default.
- W4319915619 hasConceptScore W4319915619C194544171 @default.
- W4319915619 hasConceptScore W4319915619C202751555 @default.
- W4319915619 hasConceptScore W4319915619C2779395532 @default.
- W4319915619 hasConceptScore W4319915619C2780427682 @default.
- W4319915619 hasConceptScore W4319915619C2992686903 @default.
- W4319915619 hasConceptScore W4319915619C55493867 @default.
- W4319915619 hasConceptScore W4319915619C79879829 @default.
- W4319915619 hasConceptScore W4319915619C86803240 @default.
- W4319915619 hasConceptScore W4319915619C95444343 @default.
- W4319915619 hasIssue "3" @default.
- W4319915619 hasLocation W43199156191 @default.
- W4319915619 hasLocation W43199156192 @default.
- W4319915619 hasOpenAccess W4319915619 @default.
- W4319915619 hasPrimaryLocation W43199156191 @default.
- W4319915619 hasRelatedWork W1521360838 @default.
- W4319915619 hasRelatedWork W2107571282 @default.
- W4319915619 hasRelatedWork W2760315922 @default.
- W4319915619 hasRelatedWork W2893068582 @default.
- W4319915619 hasRelatedWork W3005106094 @default.
- W4319915619 hasRelatedWork W3023076629 @default.
- W4319915619 hasRelatedWork W4224058734 @default.
- W4319915619 hasRelatedWork W4225165230 @default.
- W4319915619 hasRelatedWork W4242816820 @default.
- W4319915619 hasRelatedWork W2130483303 @default.
- W4319915619 hasVolume "122" @default.
- W4319915619 isParatext "false" @default.
- W4319915619 isRetracted "false" @default.
- W4319915619 workType "article" @default.