title: TRPC4 currents have properties similar to the pacemaker current in interstitial cells of Cajal.
abstract: Interstitial cells of Cajal (ICC) are the pacemaker cells responsible for the generation and propagation of electrical slow waves in phasic muscles of the gastrointestinal (GI) tract. The pacemaker current that initiates each slow wave derives from a calcium-inhibited, voltage-independent, nonselective cation channel. This channel in ICC displays properties similar to that reported for the transient receptor potential (TRP) family of nonselective cation channels, particularly those seen for TRPC3 and TRPC4. We have identified transcripts for TRPC4 in individually isolated ICC and have cloned the two alternatively spliced forms of TRPC4, TRPC4 alpha and TRPC4 beta, from GI muscles. TRPC4 beta is missing an 84-amino acid segment from the carboxy terminus. Expression of either form using the whole cell patch-clamp technique led to calcium-inhibited, nonselective cation channels as determined by N-methyl-D-glucamine replacement experiments and BAPTA dialysis. Expression of TRPC4 beta channels recorded at the whole cell level had characteristics similar to the nonselective cation current in ICC. The single-channel conductance of TRPC4 beta was determined to be 17.5 pS. Application of calmidazolium to cells expressing TRPC4 beta led to a significant increase in the inward current of these cells at both the whole cell and single-channel level, and currents were sensitive to block by 10 microM lanthanum, niflumic acid, and DIDS. Comparison of the properties reported for the nonselective cation current in ICC and those identified here for TRPC4 beta led us to conclude that a TRPC4-like current encodes the plasmalemmal pacemaker current in murine small intestine.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, Nevada 89557, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Walker
authors.forename: Sang Don
authors.initials: SD
authors.lastname: Koh
authors.forename: Gerard P
authors.initials: GP
authors.lastname: Sergeant
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Burton
authors.initials: B
authors.lastname: Horowitz
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002412:Cations / Q000378:metabolism; D002460:Cell Line; D004064:Digestive System / Q000166:cytology; D004068:Digestive System Physiological Phenomena; D004553:Electric Conductivity; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D009544:Niflumic Acid / Q000494:pharmacology; D010507:Periodicity; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology; D050052:TRPC Cation Channels
chemical_list: D015220:Calcium Channels; D002412:Cations; D020033:Protein Isoforms; D050052:TRPC Cation Channels; D009544:Niflumic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid