title: Basal sympathetic activity generated in neonatal mouse brainstem-spinal cord preparation requires T-type calcium channel subunit 1H.
abstract: The T-type calcium channel (T-channel) is a low-voltage-activated channel. Whether T-channels are involved in sympathetic nerve discharge (SND), with subunits α1G and α1H differentially regulating SND genesis, was explored using in vitro brainstem-spinal cord-splanchnic sympathetic nerve preparations of wild-type and genetically modified B6 mice. Applications of 10-80 μm NNC 55-0396 to block T-channels in wild-type mice reduced SND in a concentration-dependent manner. Amounts of SND were measured in units of signal-to-noise ratio for objective comparisons between mouse groups. Comparable amounts of SND were observed in wild-type and α1G(-/-) mice. However, only ∼40% of the amount of SND of that in wild-type or α1G(-/-) mice was observed in α1H(-/-) mice. Whether a diminished excitatory drive originating in the brainstem could explain a low SND in α1H(-/-) mice was evaluated by cervical cord transections. Isolated spinal cord preparations of mice with different genetic backgrounds produced comparable amounts of SND. Excitability of the spinal circuitry was further explored by bath applications of 5 mm glutamate. Glutamate applications produced a prominent SND rise in all mouse groups. The ratios of glutamate-induced SND rise were similar between wild-type and α1H(-/-) mice, but significantly higher in α1G(-/-) mice. Taken together, these results suggest that α1H in mouse brainstem is essential for the genesis of presympathetic drive, whereas α1G in mouse spinal cord is functionally inhibitory for SND genesis. We conclude that α1H and α1G T-channel subunits may differentially regulate mouse SND genesis at different levels of the neuraxis.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Chen
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Fan
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: Chun-Kuei
authors.initials: CK
authors.lastname: Su
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000502:physiology*; D003521:Cyclopropanes / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009281:Naphthalenes / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013153:Splanchnic Nerves / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D001562:Benzimidazoles; C498197:Cacna1g protein, mouse; D020747:Calcium Channels, T-Type; D003521:Cyclopropanes; D009281:Naphthalenes; C484287:NNC 55-0396; D018698:Glutamic Acid