title: Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle.
abstract: Resting membrane potential (RMP) plays an important role in determining the basal excitability of gastrointestinal smooth muscle. The RMP in colonic muscles is significantly less negative than the equilibrium potential of K(+), suggesting that it is regulated not only by K(+) conductances but by inward conductances such as Na(+) and/or Ca(2+). We investigated the contribution of nonselective cation channels (NSCC) to the RMP in human and monkey colonic smooth muscle cells (SMC) using voltage- and current-clamp techniques. Qualitative reverse transcriptase-polymerase chain reaction was performed to examine potential molecular candidates for these channels among the transient receptor potential (TRP) channel superfamily. Spontaneous transient inward currents and holding currents were recorded in human and monkey SMC. Replacement of extracellular Na(+) with equimolar tetraethylammonium or Ca(2+) with Mn(2+) inhibited basally activated nonselective cation currents. Trivalent cations inhibited these channels. Under current clamp, replacement of extracellular Na(+) with N-methyl-D-glucamine or addition of trivalent cations caused hyperpolarization. Three unitary conductances of NSCC were observed in human and monkey colonic SMC. Molecular candidates for basally active NSCC were TRPC1, C3, C4, C7, M2, M4, M6, M7, V1, and V2 in human and monkey SMC. Comparison of the biophysical properties of these TRP channels with basally active NSCC (bI(NSCC)) suggests that TRPM4 and specific TRPC heteromultimer combinations may underlie the three single-channel conductances of bI(NSCC). In conclusion, these findings suggest that basally activated NSCC contribute to the RMP in human and monkey colonic SMC and therefore may play an important role in determining basal excitability of colonic smooth muscle.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, 89557, USA. skoh@medicine.nevada.edu
authors.forename: Laura
authors.initials: L
authors.lastname: Dwyer
authors.forename: Poong-Lyul
authors.initials: PL
authors.lastname: Rhee
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lowe
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zheng
authors.forename: Lauren
authors.initials: L
authors.lastname: Peri
authors.forename: Seungil
authors.initials: S
authors.lastname: Ro
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Sang Don
authors.initials: SD
authors.lastname: Koh
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002412:Cations / Q000378:metabolism*; D003106:Colon / Q000502:physiology*; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000502:physiology; D050052:TRPC Cation Channels / Q000502:physiology*; D050053:TRPM Cation Channels / Q000502:physiology*
chemical_list: D002412:Cations; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D012964:Sodium