TRPM3

TRPM3 belongs to the melastatin subfamily of TRP channels and represents a non-selective cation channel activated by pregnenolone sulfate, osmotic pressures, and heat^[1]. Mechanistically, TRPM3 is expressed in somatosensory neurons, is frequently coexpressed with TRPA1 and TRPV1, and may contribute to noxious heat detection and heat hyperalgesia during inflammation^[2]. In disease models, gain-of-function TRPM3 variants caused increased basal activity, cellular calcium overload, and neurodevelopmental disorders with epilepsy, altered pain perception, and cerebellar involvement^[3]. Compared with related isoforms, TRPM3 exists as multiple splice variants with significantly different biophysical properties, whereas TRPM1 is linked to retinal ON-bipolar signaling and congenital stationary night blindness^[2]. For experimental applications, TM3E3 partially inhibited TRPM3-mediated ionic current and Ca²⁺ entry without affecting TRPC5, TRPV4, TRPM2, or endogenous ATP responses^[4]. Volatile anaesthetics also inhibited agonist-induced and heat-activated TRPM3 Ca²⁺ signals and currents in recombinant cells and sensory neurons^[5].