Functional role of cyclic nucleotide-gated channels in rat medial vestibular nucleus neurons.
Although cyclic nucleotide-gated (CNG) channels are expressed in numerous brain areas, little information is available on their functions in CNS neurons. The aim of the present study was to define the distribution of CNG channels in the rat medial vestibular nucleus (MVN) and their possible involvement in regulating MVN neuron (MVNn) excitability. The majority of MVNn expressed both CNG1 and CNG2 A subunits. In whole-cell current-clamp experiments carried out on brainstem slices containing the MVNn, the membrane-permeant analogues of cyclic nucleotides, 8-Br-cGMP and 8-Br-cAMP (1 mM), induced membrane depolarizations (8.9 +/- 0.8 and 9.2 +/- 1.0 mV, respectively) that were protein kinase independent. The cGMP-induced depolarization was associated with a significant decrease in the membrane input resistance. The effects of cGMP on membrane potential were almost completely abolished by the CNG channel blockers, Cd(2+) and L-cis-diltiazem, but they were unaffected by blockade of hyperpolarization-activated cyclic nucleotide-gated channels. In voltage-clamp experiments, 8-Br-cGMP induced non-inactivating inward currents (-22.2 +/- 3.9 pA) with an estimated reversal potential near 0 mV, which were markedly inhibited by reduction of extracellular Na(+) and Ca(2+) concentrations. Membrane depolarization induced by CNG channel activation increased the firing rate of MVNn without changing the action potential shape. Collectively, these findings provide novel evidence that CNG channels affect membrane potential and excitability of MVNn. Such action should have a significant impact on the function of these neurons in sensory-motor integration processes. More generally, it might represent a broad mechanism for regulating the excitability of different CNS neurons.
Institute of Human Physiology, Medical School, Catholic University S. Cuore, I-00168 Rome, Italy.
Maria Vittoria
MV
Podda
Marcello
M
D'Ascenzo
Lucia
L
Leone
Roberto
R
Piacentini
Gian Battista
GB
Azzena
Claudio
C
Grassi
D000200:Action Potentials; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014726:Vestibular Nuclei / Q000378:metabolism*
C518239:Cnga2 protein, rat; D054815:Cyclic Nucleotide-Gated Cation Channels; D021122:Protein Subunits; D000242:Cyclic AMP; D006152:Cyclic GMP