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Beta2 and beta4 subunits of BK channels confer differential sensitivity to acute modulation by steroid hormones.
- Source :
-
Journal of neurophysiology [J Neurophysiol] 2006 May; Vol. 95 (5), pp. 2878-88. Date of Electronic Publication: 2006 Jan 25. - Publication Year :
- 2006
-
Abstract
- Membrane-associated receptors for rapid, steroidal neuromodulation remain elusive. Estradiol has been reported to facilitate activation of voltage- and Ca(2+)-dependent BK potassium channels encoded by Slo, if associated with beta1 subunits. We show here that 1) multiple members of the beta family confer sensitivity to multiple steroids on BK channels, 2) that beta subunits differentiate between steroids, and 3) that different betas have distinct relative preferences for particular steroids. Expressed in HEK 293 cells, inside-out patches with channels composed of Slo-alpha alone showed no steroid sensitivity. Cells expressing alphabeta4 exhibited potent, rapid, reversible, and dose-dependent potentiation by corticosterone (CORT; a glucocorticoid), and were potentiated to a lesser degree by other sex and stress steroids. In contrast, alphabeta2 channels were potentiated more strongly by dehydroepiandrosterone (DHEA; an enigmatic, stress-related adrenal androgen), and to a lesser extent by CORT, estradiol, testosterone, and DHEA-S. Cholesterol had no effect on any BK channel compositions tested. Conductance-voltage plots of channels composed of alpha plus beta2 or beta4 subunits were shifted in the negative direction by steroids, indicating greater activation at negative voltages. Thus our results argue that the variety of Slo-beta subunit coexpression patterns occurring in vivo expands the repertoire of Slo channel gating in yet another dimension not fully appreciated, rendering BK gating responsive to dynamic fluctuations in a multiple of steroid hormones.
- Subjects :
- Animals
Blotting, Northern methods
Cells, Cultured
Chromaffin Cells drug effects
Chromaffin Cells physiology
Chromaffin Cells radiation effects
Corticosterone pharmacology
Dehydroepiandrosterone pharmacology
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Drug Interactions
Electric Stimulation methods
Humans
Large-Conductance Calcium-Activated Potassium Channel beta Subunits classification
Large-Conductance Calcium-Activated Potassium Channel beta Subunits genetics
Membrane Potentials physiology
Patch-Clamp Techniques methods
Protein Subunits physiology
RNA, Messenger biosynthesis
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction methods
Steroids chemistry
Steroids classification
Transfection methods
Large-Conductance Calcium-Activated Potassium Channel beta Subunits physiology
Membrane Potentials drug effects
Steroids pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3077
- Volume :
- 95
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of neurophysiology
- Publication Type :
- Academic Journal
- Accession number :
- 16436475
- Full Text :
- https://doi.org/10.1152/jn.01352.2005