Histamine as a Putative Transmitter of Presynaptic Inhibition: Effect onto the Ca++ Channel in Aplysia Neurons
Utilizing voltage-clamp techniques, we examined the synaptic conductance mechanism underlying presynaptic inhibition in Aplysia californica, in a circuit in which all the neural elements are identified cells. L10 is an interneuron in the abdominal ganglion, whose output to RB cells (EPSP excitatory postsynaptic potential) and LUQ cells (1PSP inhibitory postsynaptic potential) is presynaptically inhibited by stimulating cells of the L32 cluster. Stimulation of L32 cells causes a slow inhibitory synaptic potential onto L10 which is associated with an apparent increased membrane conductance. Among various putative transmitters tested, histamine was most effective in mimicking the postsynaptic effects of L32 cells onto L10: (1) decrease of the voltage-dependent Ca++ current, and (2) increase of a voltage-dependent K+ current. Both effects inhibit transmitter release from DO either directly by decreasing the amount of Ca++ entering during spike depolarization or indirectly by hyperpolarizing L10 and decreasing the amplitude and duration of spikes in L10. The response of L10 to histamine and the L32-L10 IPSP could be reversibly blocked by cimetidine, a histamine antagonist in Aplysia. In addition, the synaptic vesicles in identified L32 cells (using horseradish peroxidase as a marker) are morphologically strikingly similar to vesicles in cell C2, an identified histaminergic neuron in Aplysia. The vesicle distribution in L32 cell varicosities also is identical to the vesicle distribution in C2. These results support our model of presynaptic inhibition which states that presynaptic inhibition is caused by a direct transmitter-mediated reduction In presynaptic Ca++ current.