title: Neuromedin C decreases potassium conductance and increases a non-specific conductance in rat suprachiasmatic neurones in brain slices in vitro.
abstract: Whole-cell recordings were made, in both current and voltage clamp, from suprachiasmatic neurones maintained in coronal rat brain slices. In current clamp doses of 10 and 100 nM neuromedin C (NMC) were shown to increase basal firing rate in 9 out of 32 neurones. The excitatory responses to 100 nM NMC were accompanied by small increases in neuronal input resistance (25.0 +/- 9.9% in 4 out of 7 neurones tested) and depolarisations of membrane potential (9.8 +/- 3.4 mV in 4 out of 7 neurones tested). However, 10 nM NMC caused no changes in either neuronal input resistance or membrane potential despite the clear increases in neuronal firing rate. When voltage-clamped at -60 mV, 100 nM NMC induced an inward current of 14.8 +/- 1.2 pA in 46 of 210 neurones. The NMC-induced inward current was shown to be unaffected by perfusion with 1 microM tetrodotoxin (TTX). The inward current recorded at -60 mV was typically associated with a decrease in membrane conductance. Construction of current-voltage relationships in the absence and presence of 100 nM NMC showed that with the majority of the NMC-sensitive neurones the inward current either reversed polarity close to the potassium reversal potential or decreased at hyperpolarised potentials. This reversal potential was shifted to more depolarised potentials when the extracellular concentration of potassium was increased. The NMC-induced inward current was unaffected by reduction of the extracellular concentration of sodium or by addition of 0.2 mM cadmium. In potassium-free conditions, in both the dialysing pipette solution and perfusing saline, NMC was still able to induce an inward current. The additional reduction of the extracellular concentration of sodium, whilst recording in potassium-free conditions, was also unable to abolish the inward current. Recordings made with an electrode containing the non-hydrolysable guanosine triphosphate analogue, guanosine 5'-thio-triphosphate, resulted in NMC-induced inward currents which failed to recover to baseline. It is concluded that NMC excites a subpopulation of suprachiasmatic neurones by decreasing a resting potassium conductance and increasing a non-specific conductance, via a G-protein link.
authors.affiliation: Parke Davis Neuroscience Research Center, University of Cambridge Forvie Site, UK.
authors.forename: T
authors.initials: T
authors.lastname: Reynolds
authors.forename: R D
authors.initials: RD
authors.lastname: Pinnock
mesh_terms: D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000502:physiology*
chemical_list: D010446:Peptide Fragments; D015221:Potassium Channels; C040794:neuromedin C; D001839:Bombesin