Excitatory effect of noradrenaline on pacemaker cells in spinal cord primary cultures.
Intracellular recordings were made from dissociated fetal mouse spinal cord neurons in primary culture. One particular type of neuron, with a large cell body (40-50 micron) and three to five thick neurites, exhibited rhythmic electrical activity of two different types, consisting of either spontaneous burst discharges or tonic action potential firing. Both types of activity appeared to be triggered by an endogenous membrane potential oscillation. Micropressure application of noradrenaline (10(-5) M in the delivery pipette) onto the surface of such cells evoked, in a dose-dependent manner, an increase in the input resistance with a depolarization of the membrane potential. The response to NA was potential-dependent. The maximum change in input resistance was observed at membrane potential values between -60 mV and -45 mV and the response was suppressed at membrane potentials lower than -80 mV. No modification of the response was observed in the presence of 50 mM of tetraethylammonium. The extrapolated reversal potential, close to -90 mV, was modified by increasing extracellular K+ concentration and unaltered by increasing the intracellular Cl- concentration. The decrease in K+ conductance induced by noradrenaline was Ca2+-dependent and reversibly suppressed by Ba2+ (6 mM) and Cd2+ (0.1 mM). This response to noradrenaline was suppressed in the presence of muscarine (10 microM) suggesting that noradrenaline decreases a K+ conductance related to M current. The noradrenaline evoked increase in input resistance was mediated by activation of an alpha 1 receptor site. Prazosin, an alpha 1 antagonist and phentolamine, an alpha 1 alpha 2 antagonist, reversibly suppressed the response in a competitive manner. Yohimbine, a competitive alpha 2 antagonist, also blocked the response, but in a noncompetitive manner. Clonidine, an alpha 2 agonist, isoprenaline, a beta agonist and L-alprenolol, a beta antagonist, had no effect.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects*; D002478:Cells, Cultured; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology* / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D007473:Ion Channels; D011942:Receptors, Adrenergic, alpha; D013757:Tetraethylammonium Compounds; D013779:Tetrodotoxin; D009638:Norepinephrine; D011224:Prazosin