An analysis of histamine-induced inhibitory response in molluscan neurons.

Mechanisms of the histamine-induced inhibitory response (the H2-response) in neurons of the marine mollusc Onchidium, were further investigated following the preceding paper. The H2-response in normal saline was blocked by ouabain, but the response recovered after a short exposure to Na-free solution containing ouabain. The recovery was only transient in the continuous presence of ouabain. When external Na was reduced to about 1/8 normal concentration (60 mM), the H2-response became sensitive to removal of external Ca, but insensitive to ouabain. The suppressing effect of Ca removal and the recovery by Ca readmission appeared very slowly. However, in about 1/3 normal Na concentration (150 mM) the H2-response was suppressed by removal of the Ca, only in the presence of ouabain. The Na-gradient may be regulated by the ouabain-insensitive transportk, such as a Na-Ca exchange in addition to the ouabain-sensitive Na-pump. The Na-Ca exchange probably dominates over the ouabain-sensitive Na-pump only when passive Na-influx is reduced in a low external Na concentration. The H2-response was markedly inhibited by DNP (5 X 10(-4)M) and cyanide (2 X 10(-3)M), while the hyperpolarization produced by glutamate, which was accompanied by a large reduction of membrane resistance, was not affected by these metabolic inhibitors. Over a wide range of external Na concentrations, the membrane potential was lower in presence than in the absence of external Ca. This may be explained by the hypothesis that there is an electrogenic Na-Ca exchange in which Ca-influx is coupled with Na-efflux. According to a similar hypothesis, the H2-response is produced by the transport system in which Ca-efflux is coupled with Na-influx and the system is controlled by the transmembrane Na gradient.