title: Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells.
abstract: Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) andCalhm1knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells fromCalhm1KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent inCalhm1KO cells, suggesting that CALHM1 contributes to all of these currents.Calhm1deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However,Calhm1deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials.NEW & NOTEWORTHYCALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1.Calhm1deletion was without effects on resting membrane properties or voltage-gated Na+and K+channels but contributed modestly to the kinetics of action potentials.
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and zma@mail.med.upenn.edu.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and.
authors.forename: Wint Thu
authors.initials: WT
authors.lastname: Saung
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and.|Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Foskett
mesh_terms: D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012964:Sodium / Q000378:metabolism*; D013650:Taste Buds / Q000378:metabolism / Q000502:physiology*
chemical_list: C575356:CALHM1 protein, mouse; D015220:Calcium Channels; D007473:Ion Channels; D000255:Adenosine Triphosphate; D012964:Sodium
keywords: ATP release channel; taste bud; voltage clamp; voltage-gated ion channel