Histamine actions and comparison with substance P effects in trigeminal neurons

Abstract

Applications of histamine to neurons in slices of trigeminal root ganglia (guinea-pig) produced slow changes in the steady-state membrane potentials and input resistances. Several types of response to histamine could be distinguished: (i) depolarizations accompanied by an increase, a decrease or no change in input resistance; (ii) small hyperpolarizations associated with a decreased or unchanged input resistance; and (iii) combined hyper- and depolarizations. The amplitudes of all response types waned during prolonged applications of histamine. The depolarizing responses to histamine appeared to depend on the presence of outward rectification in the region of the initial resting potential; neurons which possessed linear current-voltage relationships near the initial resting potential were depolarized by > 10 mV, whereas neurons with outward rectification near rest showed smaller depolarizing responses. Histamine also reduced the magnitude of the long-duration spike afterhyperpolarizations which had been attributed in the ganglionic neuron to a Ca 2+-activated K + conductance mechanism. Application of substance P, another possible neuromodulator in the trigeminal system, had depolarizing, desensitizing actions similar to those of histamine. Substance P and histamine did not cross-desensitize during prolonged applications. Histamine-induced depolarizations were unchanged under zero Mg 2+ extracellular conditions, in contrast to a dependency of the substance P-induced effects on external Mg 2+. Based on the histamine-induced changes in perikaryal potential and input resistance in trigeminal root ganglion neurons it is suggested that: (i) the ionic mechanisms by which histamine produces its effects are likely to be independent of the substance P mechanism of action; (ii) the hyperpolarizing response may result from an increased K + conductance; (iii) the depolarizing response may result from a decreased K + conductance and a concurrent increase in the conductance to ions other than Ca 2+ or Mg 2+; (iv) the multiphasic responses can be interpreted as a superposition of (ii) and (iii) above. Furthermore, we speculate that histamine released from mast cells, may be an intraganglionic neuromodulator of sensory transmission.