TY - JOUR T1 - Neuron type-specific mechanical regulation of voltage-gated Ca<sup>2+</sup> channels and excitability in hippocampal and trigeminal ganglion neurons JF - bioRxiv DO - 10.1101/123364 SP - 123364 AU - Sisi liu AU - Yang Yu AU - Xiaoan Wu AU - Liying Huang AU - Yuchen Qi AU - Lin-Hua Jiang AU - Hucheng Zhao Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/03/123364.abstract N2 - Increasing evidence suggests that the mechanical properties of extracellular matrix regulate central and peripheral neuronal functions. We thus investigated the CaV channels in hippocampal and trigeminal ganglion (TG) neurons cultured on substrates with different stiffness. Patch-clamp current recordings showed that stiff substrate augmented the CaV channel currents in hippocampal and TG neurons and additionally induced a leftward shift in the voltage-dependent channel activation curve in small TG neurons. Combination with using selective channel blockers revealed that substrate stiffness preferentially regulated the N-type channel current in hippocampal and medium TG neurons but the T-type channel current in small TG neurons. Current-clamp recordings further demonstrated that stiff substrate enhanced the excitability of small TG neurons, which was ablated by blocking the T-type channel. Treatment of neurons on the stiff substrate with low-dose blebbistatin reduced both the N-type channel current in hippocampal and medium TG neurons and the T-type channel current in small TG neurons to the levels in neurons on the soft substrate, whereas treatment of neurons on the soft substrate with calcium A increased both the N-type channel current in hippocampal and medium TG neurons and the T-type channel current in small TG neurons to the levels in neurons on the stiff substrate, thus consistently supporting critical involvement of actomyosin in mechanical sensing. Taken together, our results reveal neuron type-specific mechanical regulation of the Cav channels and excitability in the nervous system. Such information is useful for neural tissue engineering and regeneration. ER -