title: Activation of steroid-sensitive TRPM3 channels potentiates glutamatergic transmission at cerebellar Purkinje neurons from developing rats.
abstract: The functional implications of transient receptor potential melastatin 3 (TRPM3) activation, the most recently described member of the melastatin subfamily of cation permeable TRP channels, have begun to be elucidated in recent years. The discovery of TRPM3 activation by the steroid pregnenolone sulfate (PregS) has shed new light on the physiological role of this channel. For example, TRPM3 activation enhances insulin secretion from β pancreatic cells, induces contraction of vascular smooth muscle, and is also involved in the detection of noxious heat. Although TRPM3 expression has been detected in several regions of the developing and mature brain, little is known about the roles of TRPM3 in brain physiology. In this study, we demonstrate the abundant expression of TRPM3 steroid-sensitive channels in the developing cerebellar cortex. We also show that TRPM3-like channels are expressed at glutamatergic synapses in neonatal Purkinje cells. We recently showed that PregS potentiates spontaneous glutamate release onto neonatal Purkinje cells during a period of active glutamatergic synapse formation; we now show that this effect of PregS is mediated by TRPM3-like channels. Mefenamic acid, a recently discovered TRPM3 antagonist, blocked the effect of PregS on glutamate release. The PregS effect on glutamate release was mimicked by other TRPM3 agonists (nifedipine and epipregnanolone sulfate) but not by a TRMP3-inactive steroid (progesterone). Our findings identify TRPM3 channels as novel modulators of glutamatergic transmission in the developing brain.
authors.affiliation: Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131-0001, USA.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Zamudio-Bulcock
authors.forename: Julie
authors.initials: J
authors.lastname: Everett
authors.forename: Christian
authors.initials: C
authors.lastname: Harteneck
authors.forename: C Fernando
authors.initials: CF
authors.lastname: Valenzuela
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011284:Pregnenolone / Q000494:pharmacology*; D021381:Protein Transport / Q000235:genetics; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D050053:TRPM Cation Channels / Q000378:metabolism* / Q000502:physiology
chemical_list: D050053:TRPM Cation Channels; C533867:TRPM3 protein, rat; C018370:pregnenolone sulfate; D018698:Glutamic Acid; D011284:Pregnenolone