Differential expression and alternative splicing of TRP channel genes in smooth muscles

Abstract

Nonselective cation channels (NSCC) are targets of excitatory agonists in smooth muscle, representing the nonselective cation current I cat. Na+ influx through NSCC causes depolarizations and activates voltage-dependent Ca2+ channels, resulting in contraction. The molecular identity of I cat in smooth muscle has not been elucidated; however, products of the transient receptor potential (TRP) genes have characteristics similar to native I cat. We have determined the levels of TRP transcriptional expression in several murine and canine gastrointestinal and vascular smooth muscles and have analyzed the alternative processing of these transcripts. Of the seven TRP gene family members, transcripts for TRP4, TRP6, and TRP7 were detected in all murine and canine smooth muscle cell preparations. TRP3 was detected only in canine renal artery smooth muscle cells. The full-length cDNAs for TRP4, TRP6, and TRP7, as well as one splice variant of TRP4 and two splice variants of TRP7, were cloned from murine colonic smooth muscle. Quantitative RT-PCR determined the relative amounts of TRP4, TRP6, and TRP7 transcripts, as well as that of the splice variants, in several murine smooth muscles. TRP4 is the most highly expressed, while TRP6 and TRP7 are expressed at a lower level in the same tissues. Splice variants for TRP7, deleted for exons encoding amino acids including transmembrane segment S1, predominated in murine smooth muscles, while the full-length form of the transcript was expressed in canine smooth muscles.