Alternatively Spliced Human TREK-1 Variants Alter TREK-1 Channel Function and Localization

Area of Science:

• Physiology
• Molecular Biology
• Obstetrics

Background:

• TREK-1 (a potassium channel) is present in the myometrium and its decreased expression near term is linked to uterine quiescence.
• Alternative splicing of TREK-1 leads to variants, particularly in women experiencing spontaneous preterm birth (<37 weeks).

Purpose of the Study:

• To investigate the functional impact of TREK-1 variants on TREK-1 channel expression and activity.
• To determine if TREK-1 variants contribute to the pathophysiology of preterm labor.

Main Methods:

• Immunofluorescence, cell surface assays, Western blots, and patch clamp electrophysiology were used.
• TREK-1 and its variants were expressed in HEK293T cells for functional analysis.

Main Results:

• Coexpression of TREK-1 with its variants reduced TREK-1 membrane expression and suppressed channel function.
• Individual variants showed significantly decreased channel properties compared to full-length TREK-1.
• Basal and acidosis-activated TREK-1 currents were substantially reduced (∼64% and ∼77%, respectively) when coexpressed with variants.

Conclusions:

• TREK-1 variants are associated with reduced TREK-1 activity in the myometrium.
• These findings suggest a pathological role for TREK-1 variants in the development of preterm labor.