title: Intermediate-conductance calcium-activated potassium channels in enteric neurones of the mouse: pharmacological, molecular and immunochemical evidence for their role in mediating the slow afterhyperpolarization.
abstract: Calcium-activated potassium channels are critically important in modulating neuronal cell excitability. One member of the family, the intermediate-conductance potassium (IK) channel, is not thought to play a role in neurones because of its predominant expression in non-excitable cells such as erythrocytes and lymphocytes, in smooth muscle tissues, and its lack of apparent expression in brain. In the present study, we demonstrate that IK channels are localized on specific neurones in the mouse enteric nervous system where they mediate the slow afterhyperpolarization following an action potential. IK channels were localized by immunohistochemistry on intrinsic primary afferent neurones, identified by their characteristic Dogiel type II morphology. The slow afterhyperpolarization recorded from these cells was abolished by the IK channel blocker clotrimazole. RT-PCR and western analysis of extracts from the colon revealed an IK channel transcript and protein identical to the IK channel expressed in other cell types. These results indicate that IK channels are expressed in neurones where they play an important role in modulating firing properties.
authors.affiliation: Department of Anatomy and Cell Biology and Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia. cbneylon@unimelb.edu.au
authors.forename: Craig B
authors.initials: CB
authors.lastname: Neylon
authors.forename: Kulmira
authors.initials: K
authors.lastname: Nurgali
authors.forename: Billie
authors.initials: B
authors.lastname: Hunne
authors.forename: Heather L
authors.initials: HL
authors.lastname: Robbins
authors.forename: Stephen
authors.initials: S
authors.lastname: Moore
authors.forename: Mao Xiang
authors.initials: MX
authors.lastname: Chen
authors.forename: John B
authors.initials: JB
authors.lastname: Furness
mesh_terms: D000818:Animals; D064032:Calbindin 2; D003022:Clotrimazole / Q000494:pharmacology*; D003106:Colon / Q000166:cytology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
chemical_list: D064032:Calbindin 2; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496925:Kcnn4 protein, mouse; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; D003022:Clotrimazole