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Characterization of the molecular and electrophysiological properties of the T‐type calcium channel in human myometrium
Author(s) -
Blanks Andrew M.,
Zhao ZhengHang,
Shmygol Anatoly,
BruMercier Gilles,
Astle Shirley,
Thornton Steven
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.132126
Subject(s) - contractility , t type calcium channel , electrophysiology , myometrium , voltage dependent calcium channel , calcium channel , patch clamp , contraction (grammar) , membrane potential , calcium , intracellular , medicine , l type calcium channel , endocrinology , calcium in biology , voltage clamp , biophysics , biology , chemistry , microbiology and biotechnology , uterus
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 Ca v 3.1(α1G), Ca v 3.2(α1H), and Ca v 3.3(α1I). QRT‐PCR, immunohistochemistry, electrophysiology and invitro contractility were performed on human myometrial samples from term, preterm, labour and not in labour. QRT‐PCR analysis of Ca v 3.1, Ca v 3.2 and Ca v 3.3 demonstrated expression of Ca v 3.1 and Ca v 3.2 with no significant change ( P > 0.05) associated with gestation or labour status. Immunohistochemistry localized Ca v 3.1 to myometrial and vascular smooth muscle cells whilst Ca v 3.2 localized to vascular endothelial cells and invading leucocytes. Voltage clamp studies demonstrated a T‐type current in 55% of cells. Nickel block of T‐type current was voltage sensitive (IC 50 of 118.57 ± 68.9 μ m at −30 mV). Activation and inactivation curves of I Ca 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 −80 mV elicited rebound calcium spikes that were blocked reversibly by 100 μ m nickel. Contractility studies demonstrated a reversible decrease in contraction frequency during application of 100 μ m nickel ( P < 0.05). We conclude that the primary T‐type subunit expressed in some MSMCs is Ca v 3.1. We found that application of 100 μ m nickel to spontaneously contracting human myometrium reversibly slows contraction frequency.