An inward current induced by a putative cyclic nucleotide-gated channel in rat cerebellar Purkinje neurons

The roles of cyclic nucleotide-gated (CNG) channels in sensory transduction have long been recognized. More recent studies found that CNG channels are distributed in multiple brain regions involved in memory and learning, including the cortex, hippocampus and cerebellum. These findings suggest that their functions are not limited to sensory perception, but also to neuronal plasticity phenomena, such as long-term potentiation (LTP) and long-term depression (LTD). Our studies using immunostaining have shown that there is a prominent specific expression of CNG channels in cerebellar Purkinje neurons. In order to demonstrate and characterize these CNG channels, we employed whole-cell patch technique to probe their functional expression in the cerebellar Purkinje neurons in brain slices prepared from 3 weeks old Sprague-Dawley rats. Bath application of the membrane permeable analog of cGMP, 8-Br-cGMP (1mM), consistently elicited an inward current of 156±14pA (n=14) in these neurons which were voltage-clamped at –70mV. The current was washable and repeatable. An inward current could also be induced by 8-Br-cAMP (1mM), a membrane permeable analog of another cyclic nucleotide, cAMP. To eliminate the possible contribution of protein kinase G (PKG) in mediating the inward current, 8-Br-cGMP was applied in the presence of KT5823 (2 ?m), a specific PKG inhibitor, in the internal solution. In this case, a comparable inward current was still evoked (197±31pA, n=6, p>0.05). In conclusion, these characteristics are consistent with those of CNG channels. This finding strengthens the speculation that CNG channels are expressed in the cerebellum and may contribute to neuronal plasticity phenomena of the cerebellum such as LTP and LTD.