Identification and Electrophysiological Characteristics of Isoforms of T-type Calcium Channel Cav3.2 Expressed in Pregnant Human Uterus

Electrophysiological characteristics were compared among four cloned human α1H isoforms transcripted by alternative splicings of exons 25B and 26 [Δ25B/+26 (native form; α1H-a), Δ25B/Δ?6 (α1H-b), +25B/Δ26, and +25B/+26] in the intracellular loop between domains III and IV (III-IV linker) of a human T-type calcium channel (Ca v 3.2). The native isoform Δ25B/+26 predominated in ovary and non-pregnant uterus, while isoform Δ25B/Δ26 (α1H-b) predominated in pregnant uterus and testis. Expressions of the newly identified +25B/Δ26 and +25B/+26 isoforms were greater in the uterus at gestation than in the non-pregnant uterus. When expressed in Xenopus laevis oocytes, all isoforms produced transient inward currents with low voltage-dependent activation and inactivation characterized in typical T-type Ca 2+ currents. Each isoform possessing exon 25B (+25B/?Δ26 or +25B/+26) showed current activation and inactivation at a more negative membrane potential than the respective isoform (Δ25B/Δ26 or Δ25B/+26) lacking it. Moreover, the current activation and inactivation rates were faster for the two isoforms possessing exon 25B than for the respective isoforms lacking it. By itself, exon 26 seemed not to affect any electrophysiological characteristics. Increasing the net positive charge (relative to the native form), as occurred in isoforms Δ25B/Δ26, +25B/Δ26, and +25B/+26, caused recovery from short-term inactivation to become faster. Our results show that molecular-structure variations within the III-IV linker influence the voltage-dependence and kinetics of both activation and inactivation. Although the role of T-type Ca 2+ channels in uterine tissue remains unknown, changes in the uterine expression of these α1H isoforms may influence physiological functions during pregnancy.