title: Novel coupling between TRPC-like and KNa channels modulates low threshold spike-induced afterpotentials in rat thalamic midline neurons.
abstract: Neurons in thalamic midline and paraventricular nuclei (PVT) display a unique slow afterhyperpolarizing potential (sAHP) following the low threshold spike (LTS) generated by activation of their low voltage Ca(2+) channels. We evaluated the conductances underlying this sAHP using whole-cell patch-clamp recordings in rat brain slice preparations. Initial observations recorded in the presence of TTX revealed a marked dependency of the LTS-induced sAHP on extracellular Na(+): replacing Na(+) with TRIS(+) in the external medium eliminated the LTS-induced sAHP; substitution of Na(+) with either Li(+) or choline(+) in the external medium resulted in a gradual loss of the sAHP and its replacement with a prolonged slow afterdepolarizing potential (sADP). The LTS-induced sAHP was reduced by quinidine and potentiated by loxapine, suggesting involvement of KNa-like channels. Canonical transient receptor potential (TRPC) channels were considered the source for Na(+) based on observations that the sAHP was suppressed by nonselective TRPC channel blockers (2-APB, flufenamic acid and ML204) but unchanged in the presence of TRPV1 channel blocker (SB-366791). In addition, after replacement of Na(+) with Li(+), the isolated LTS-induced sADP was significantly suppressed in the presence of 2-APB or ML204, after replacement of extracellular Ca(2+) with Sr(2+), and by intracellular Ca(2+) chelation with EGTA, data that collectively suggest involvement of Ca(2+)-activated TRPC-like conductances containing TRPC4/5 subunits. The isolated LTS-induced sADP also exhibited a strong voltage dependency, decreasing at hyperpolarizing potentials, further support for involvement of TRPC4/5 subunits. This sADP exhibited neurotransmitter receptor sensitivity, with suppression by 5-CT, a 5-HT7 receptor agonist, and enhancement by the neuropeptide orexin A. These data suggest that LTS-induced slow afterpotentials reflect a simultaneous interplay between KNa and TRPC-like conductances, novel for midline thalamic neurons.
authors.affiliation: Neuroscience Program, Ottawa Hospital Research Institute and Department of Medicine, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario K1Y 4E9, Canada.
authors.forename: Miloslav
authors.initials: M
authors.lastname: Kolaj
authors.affiliation: Neuroscience Program, Ottawa Hospital Research Institute and Department of Medicine, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario K1Y 4E9, Canada.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Neuroscience Program, Ottawa Hospital Research Institute and Department of Medicine, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario K1Y 4E9, Canada. Electronic address: lprenaud@ohri.ca.
authors.forename: Leo P
authors.initials: LP
authors.lastname: Renaud
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D020644:Midline Thalamic Nuclei / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D000068797:Orexins; D018408:Patch-Clamp Techniques; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D020747:Calcium Channels, T-Type; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D011985:Receptors, Serotonin; D015222:Sodium Channels; D050052:TRPC Cation Channels; C104425:serotonin 7 receptor; D012964:Sodium; D002118:Calcium
keywords: Low-threshold spike; Midline thalamus; Sodium-activated potassium conductance; TRPC-like conductance