NDLI: Mechanisms underlying regional differences in the Ca2+ sensitivity of BKCa current in arteriolar smooth muscle

Content Provider	PubMed Central
Author	Yang, Yan Sohma, Yoshiro Nourian, Zahra Ella, Srikanth R. Min, Li Stupica, Aaron Korthuis, Ronald J. Davis, Michael J. Braun, Andrew P. Hill, Michael A.
Copyright Year	2013
Abstract	β1-Subunits enhance the gating properties of large-conductance Ca2+-activated K+ channels (BKCa) formed by α-subunits. In arterial vascular smooth muscle cells (VSMCs), β1-subunits are vital in coupling SR-generated Ca2+ sparks to BKCa activation, affecting contractility and blood pressure. Studies in cremaster and cerebral VSMCs show heterogeneity of BKCa activity due to apparent differences in the functional β1-subunit:α-subunit ratio. To define these differences, studies were conducted at the single-channel level while siRNA was used to manipulate specific subunit expression. β1 modulation of the α-subunit Ca2+ sensitivity was studied using patch-clamp techniques. BKCa channel normalized open probability (NP o) versus membrane potential (V m) curves were more left-shifted in cerebral versus cremaster VSMCs as cytoplasmic Ca2+ was raised from 0.5 to 100 μm. Calculated V 1/2 values of channel activation decreased from 72.0 ± 6.1 at 0.5 μm Ca2+ i to −89 ± 9 mV at 100 μm Ca2+ i in cerebral compared with 101 ± 10 to −63 ± 7 mV in cremaster VSMCs. Cremaster BKCa channels thus demonstrated an ∼2.5-fold weaker apparent Ca2+ sensitivity such that at a value of V m of −30 mV, a mean value of [Ca2+]i of 39 μm was required to open half of the channels in cremaster versus 16 μm[Ca2+]i in cerebral VSMCs. Further, shortened mean open and longer mean closed times were evident in BKCa channel events from cremaster VSMCs at either −30 or 30 mV at any given [Ca2+]. β1-Subunit-directed siRNA decreased both the apparent Ca2+ sensitivity of BKCa in cerebral VSMCs and the appearance of spontaneous transient outward currents. The data are consistent with a higher ratio of β1-subunit:α-subunit of BKCa channels in cerebral compared with cremaster VSMCs. Functionally, this leads both to higher Ca2+ sensitivity and NP o for BKCa channels in the cerebral vasculature relative to that of skeletal muscle.
Related Links	http://dx.doi.org/10.1113/jphysiol.2012.241562
Ending Page	1293
Page Count	17
Starting Page	1277
File Format	PDF
ISSN	14697793
e-ISSN	14697793
Journal	The Journal of Physiology
Issue Number	Pt 5
Volume Number	591
Language	English
Publisher	Blackwell Science Inc
Publisher Date	2013-03-01
Access Restriction	Open
Rights Holder	Blackwell Science Inc
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Sports Science

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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