Excitatory effect of serotonin on pacemaker neurons in spinal cord cell culture

Intracellular recordings were made from fetal mouse spinal cord neurons in primary culture. One type of neuron, with large somata (40-50 microns diameter) and thick neurites exhibited endogenous bursting or beating pacemaker electrical activity. Noradrenaline depolarized this type of neuron by decreasing an M-like conductance. Micropressure application of serotonin (10(-5) M in the delivery pipette) onto the surface of pacemaker neurons evoked a depolarization of the membrane potential in a dose-dependent manner with an increased input resistance. No such response was observed with other types of spinal cord neurons in culture. The response to serotonin was partially voltage-dependent. The serotonin-induced depolarization reversed at holding potential close to -100 mV. However, the input resistance variation evoked by serotonin increased exponentially when membrane potential was depolarized. The reversal potential was modified by increasing extracellular K+ concentration and it was unaltered by increasing the intracellular Cl- concentration. The decrease in K+ conductance induced by serotonin was not suppressed by the application of tetraethylammonium (50 mM) or 4-aminopyridine (10 mM). Furthermore, application of Ba2+ (6 mM) or Cd2+ (0.1 mM) had no effect on this response, suggesting that the depolarization evoked by serotonin application was not calcium-dependent. The serotonin evoked increase in input resistance was mediated by activation of a 5-HT1A-like receptor site. Spiperone, a 5-HT1A antagonist reversibly blocked the response. Methiothepin, a 5-HT1-5-HT2 antagonist (10(-3) M); cocaine, a 5-HT3 antagonist (10(-3) M); ketanserin, a 5-HT2 antagonist (10(-3) M); and prazosin, an alpha 1 antagonist (10(-3) M) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)