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¹ Clinical Sciences Research Institute, Division of Clinical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK

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_v3.1(1G), Ca_v3.2(1H), and Ca_v3.3(1I). 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_v3.1, Ca_v3.2 and Ca_v3.3 demonstrated expression of Ca_v3.1 and Ca_v3.2 with no significant change (P > 0.05) associated with gestation or labour status. Immunohistochemistry localized Ca_v3.1 to myometrial and vascular smooth muscle cells whilst Ca_v3.2 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 (IC₅₀ of 118.57 ± 68.9 µM 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 µM nickel. Contractility studies demonstrated a reversible decrease in contraction frequency during application of 100 µM nickel (P < 0.05). We conclude that the primary T-type subunit expressed in some MSMCs is Ca_v3.1. We found that application of 100 µM nickel to spontaneously contracting human myometrium reversibly slows contraction frequency.

(Received 21 March 2007; accepted after revision 16 April 2007; first published online 19 April 2007)
Corresponding author A. M. Blanks: Clinical Science Research Institute, Division of Clinical Sciences, Warwick Medical School, Coventry CV4 7AL, UK. Email: andrew.blanks{at}warwick.ac.uk

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