Histaminergic effects on the frequency of repetitive spike firing in rat insular cortex

The insular cortex (IC) processes multimodal sensory information including gustatory, visceral, nociceptive, and thermal sensation, and is considered to play a role in the regulation of homeostasis. The IC receives dense histaminergic projection from the tuberomamillary nucleus in the hypothalamus, and recent studies have demonstrated that the blockage of histaminergic receptors impairs physiological functions in the IC. However, little is known about the effects of histamine on the electrophysiological properties of the IC. To explore the effects of histamine on the subthreshold responses and action potential properties in the IC, intracellular recording with a sharp glass electrode was obtained from IC pyramidal cells in cortical slice preparations. Application of histamine (30 μM) increased the frequency of repetitive spike firing in response to a long depolarizing current pulse injection; accompanied by an increase in input resistance. The frequency of repetitive spike firing was estimated by the slope of the frequency-current (f/I) curve. Histamine caused an increase from 23.3±2.3 Hz/nA to 40.3±4.3 Hz/nA. The histamine-induced facilitation of repetitive spike firing was blocked by pre-application of 50 μM cimetidine, an H(2) receptor antagonist, but not 30 μM pyrilamine, an H(1) receptor antagonist. R-α-methylhistamine (10 μM), an H(3) autoreceptor agonist, had little effect on the slope of the f/I curve. These results suggest that the histamine-induced facilitation of firing frequency is mediated via H(2) and not H(1) receptors. In addition, H(3) receptors have a minor role in the intrinsic membrane and firing properties of IC pyramidal cells.