Basal sympathetic activity generated in neonatal mouse brainstem-spinal cord preparation requires T-type calcium channel subunit alpha 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 alpha 1G and alpha 1H 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 mu m 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 alpha 1G-/- mice. However, only similar to 40% of the amount of SND of that in wild-type or alpha 1G-/- mice was observed in alpha 1H-/- mice. Whether a diminished excitatory drive originating in the brainstem could explain a low SND in alpha 1H-/- 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 alpha 1H-/- mice, but significantly higher in alpha 1G-/- mice. Taken together, these results suggest that alpha 1H in mouse brainstem is essential for the genesis of presympathetic drive, whereas alpha 1G in mouse spinal cord is functionally inhibitory for SND genesis. We conclude that alpha 1H and alpha 1G T-channel subunits may differentially regulate mouse SND genesis at different levels of the neuraxis.