The effects of gastrin-releasing peptide on the voltage-gated channels in rat hippocampal neurons

Abstract

Gastrin-releasing peptide (GRP) has been implicated in several aspects of physiology and behavior including digestion, cancer, lung development, and memory process. Increasing evidence in rodents shows that GRP may contribute to hippocampal circuit function. Though the central role of GRP in the brain has been established, the cellular and molecular mechanisms of its actions have not been well defined. Thus in this study, we verified the expression of GRPR in the rat hippocampal CA1 region. Then we examined the mechanisms closely related to neuronal excitability, the effects of GRP on voltage-gated ion channels in CA1 neurons using patch-clamp. The results showed that GRP could decrease voltage-gated sodium currents mainly by affecting the kinetics of recovery from the inactivated state. However, GRP enhanced both kinds of voltage-gated potassium channels, the A-type channels were more sensitive to GRP than K-type channels. In conclusion, we found that GRP could alter the voltage-gated Na⁺ and K⁺ ion channel characteristics which might be the ionic mechanisms of the physiological function of GRP in the brain.

Keywords: Gastrin-releasing peptide; Hippocampal neurons; Voltage-gated potassium channels; Voltage-gated sodium channels.