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Characterization of the molecular and electrophysiological properties of the T-type calcium channel in human myometrium
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Blanks, Andrew M., Zhao, ZhengHang Zhao, Shmygol, Anatoly, Bru-Mercier, Gilles, Astle, Shirley and Thornton, Steven (2008) Characterization of the molecular and electrophysiological properties of the T-type calcium channel in human myometrium. The Journal of Physiology, Vol.581 (No.3). pp. 915-926. doi:10.1113/jphysiol.2007.132126 ISSN 0022-3751.
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Official URL: http://dx.doi.org/10.1113/jphysiol.2007.132126
Abstract
Rises in intracellular calcium are essential for contraction of human myometrial smooth
muscle (HMSM) and hence parturition. The T-type calcium channel may play a role in
this process. The aim was to investigate the role of the T-Type calcium channel in
HMSM by characterizing mRNA expression, protein localization, electrophysiological
properties and function of the channel subunits Cav3.1(α1G), Cav3.2(α1H), and
Cav3.3(α1I). QRT-PCR, immuno-histochemistry, electrophysiology and invitro
contractility were performed on human myometrial samples from term, preterm, labour
and not in labour. QRT-PCR analysis of Cav3.1, Cav3.2 and Cav3.3 demonstrated
expression of Cav3.1 and Cav3.2 with no significant change (P>0.05) associated with
gestation or labour status. Immuno-histochemistry localized Cav3.1 to myometrial and
vascular smooth muscle cells whilst Cav3.2 localized to vascular endothelial cells and
invading leukocytes. Voltage clamp studies demonstrated a T-type current in 55% of
cells. Nickel block of T-type current was voltage sensitive (IC50 of 118.57±68.9 μM at -
30mV). Activation and inactivation curves of ICa currents in cells expressing T-type
channels overlapped demonstrating steady state window currents at the resting membrane
potential of myometrium at term. Current clamp analysis demonstrated that
hyperpolarizing pulses to a membrane potential greater than -80mV elicited rebound
calcium spikes that were blocked reversibly by 100μM nickel. Contractility studies
demonstrated a reversible decrease in contraction frequency during application of 100μM
nickel (P<0.05). We conclude that the primary T-type subunit expressed in some MSMCs
is Cav3.1. We found that application of 100 μM nickel to spontaneously contracting
human myometrium reversibly slows contraction frequency.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine > R Medicine (General) | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
Library of Congress Subject Headings (LCSH): | Myometrium, Parturition, Calcium channels | ||||
Journal or Publication Title: | The Journal of Physiology | ||||
Publisher: | Blackwell | ||||
ISSN: | 0022-3751 | ||||
Official Date: | 14 July 2008 | ||||
Dates: |
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Volume: | Vol.581 | ||||
Number: | No.3 | ||||
Page Range: | pp. 915-926 | ||||
DOI: | 10.1113/jphysiol.2007.132126 | ||||
Status: | Peer Reviewed | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Description: | Final version (published as open access). |
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