Climbing Fibres as a Source of Nitric Oxide in the Cerebellum


Dr. John Garthwaite, as above


Exposure of adult rat cerebellar slices to a moderately raised K+ concentration (15 mM) caused a large (30-fold) rise in the levels of cyclic GMP. Excitatory amino acid antagonists failed to inhibit this response, nor could it be mimicked by agonists active at a number of other transmitter receptors. It was, however, inhibited by the nitric oxide (NO) synthase antagonist, l-methylarginine (lC50= 10 μM), and also by tetrodotoxin (1 μM) implying that underlying the cyclic GMP response was an action potential-dependent formation of NO. Prelesioning of climbing fibres resulted in a loss of ∼50% of the response to K+ but failed to influence the effects of glutamate receptor agonists or the NO-donor, nitroprusside. These findings point to a new mechanism for the formation of NO in the central nervous system and suggest that, in the cerebellum, climbing fibres are a source of NO.