title: Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons.
abstract: The mammalian brain is a mechanosensitive organ that responds to different mechanical forces ranging from intrinsic forces implicated in brain morphogenesis to extrinsic forces that can cause concussion and traumatic brain injury. However, little is known of the mechanosensors that transduce these forces. In this study we use cell-attached patch recording to measure single mechanically-gated (MG) channel currents and their affects on spike activity in identified neurons in neonatal mouse brain slices. We demonstrate that both neocortical and hippocampal pyramidal neurons express stretch-activated MG cation channels that are activated by suctions of ~25mm Hg, have a single channel conductance for inward current of 50-70pS and show weak selectivity for alkali metal cations (i.e., Na(+)<K(+)<Cs(+)). Significantly, single MG channel currents activated on the soma trigger spiking/action potentials in both neocortical and hippocampal pyramidal neurons. Not all neuron types studied here expressed MG channel currents. In particular, locus coeruleus and cerebellar Purkinje neurons showed no detectable MG channel activity. Moreover their robust rhythmic spike activity was resistant to mechanical modulation. Our observation that a single MG channel current can trigger spiking predicates the need for reassessment of the long held view that the impulse output of central neurons depends only upon their intrinsic voltage-gated channels and/or their integrated synaptic input.
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales 2308, Australia; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
authors.forename: Yury A
authors.initials: YA
authors.lastname: Nikolaev
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales 2308, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dosen
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales 2308, Australia.
authors.forename: Derek R
authors.initials: DR
authors.lastname: Laver
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales 2308, Australia.
authors.forename: Dirk F
authors.initials: DF
authors.lastname: van Helden
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales 2308, Australia; Department of Neuroscience and Cell Biology, UTMB, Galveston, TX 77555, USA. Electronic address: ohamill@utmb.edu.
authors.forename: Owen P
authors.initials: OP
authors.lastname: Hamill
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001696:Biomechanical Phenomena / Q000502:physiology*; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D019579:Neocortex / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*
chemical_list: D002712:Chlorides; D002586:Cesium; C028019:cesium chloride
keywords: Action potentials; Brain; Cation channels; Mechanically-gated; Triggered