Excitability Increase Induced by β-Adrenergic Receptor-Mediated Activation of Hyperpolarization-Activated Cation Channels in Rat Cerebellar Basket Cells

Fumihito Saitow, Shiro Konishi
2000 Journal of Neurophysiology  
Saitow, Fumihito and Shiro Konishi. Excitability increase induced by ␤-adrenergic receptor-mediated activation of hyperpolarizationactivated cation channels in rat cerebellar basket cells. J Neurophysiol 84: 2026 -2034, 2000. In the preceding paper, we showed that norepinephrine (NE) enhances the spontaneous spike firings in cerebellar interneurons, basket cells (BCs), resulting in an increase in the frequency of BC-spike-triggered inhibitory postsynaptic currents (IPSCs) in Purkinje cells
more » ... , and that the effects of NE on GABAergic BCs are mediated by ␤ 2 -adrenergic receptors. This study aimed to further examine the ionic mechanism underlying the ␤-adrenoceptor-mediated facilitation of GABAergic transmission at the BC-PC synapses. Using cerebellar slices obtained from 15-to 21-dayold rats and whole cell recordings, we investigated ionic currents in the BCs and the effects of the ␤-agonist isoproterenol (ISP) as well as forskolin on the BC excitability. Hyperpolarizing voltage steps from a holding potential of Ϫ50 mV elicited a hyperpolarization-activated inward current, I h , in the BC. This current exhibited voltage-dependent activation that was accelerated by strong hyperpolarization, displaying two time constants, 84 Ϯ 6 and 310 Ϯ 40 ms, at Ϫ100 mV, and was inhibited by 20 M ZD7288. ISP and forskolin, both at 20 M, enhanced I h by shifting the activation curve by 5.9 and 9.3 mV toward positive voltages, respectively. Under the current-clamp mode, ISP produced a depolarization of 7 Ϯ 3 mV in BCs and reduced their input resistance to 74 Ϯ 6%. ISP and a cAMP analogue, Rp-cAMP-S, increased the frequency of spontaneous spikes recorded from BCs using the cell-attached mode. The I h inhibitor ZD7288 decreased the BC spike frequency and abolished the ISP-induced increase in spike discharges. The results suggest that NE depolarizes the BCs through ␤-adrenoceptor-mediated cAMP formation linking it to activation of I h , which is, at least in part, involved in noradrenergic afferentmediated facilitation of GABAergic synaptic activity at BC-PC connections in the rat cerebellum.
doi:10.1152/jn.2000.84.4.2026 pmid:11024095 fatcat:d45po3tibvfkhfckgcsd6r4dyq