THE EFFECT OF CALCITONIN GENE-RELATED PEPTIDE ON ACID-SENSING ION CHANNEL ACTIVITY IN PRIMARY CELL CULTURE OF TRIGEMINAL GANGLION NEURONS

Abstract

The local tissue acidosis of inflammatory events leads to physiological pH drop and causes headache via the activation of small-to-medium-sized trigeminal ganglion (TG) neurons. Acid sensing ion channels (ASICs) are the acidic sensor in which requiring at least pH 7.0 to cause neurotransmitter release, such as CGRP. CGRP elevates nociceptive signal by activating its receptor on large-sized neurons. However, the role of CGRP on ASICs activity has not been investigated. Moreover, the role of pH 7.0 on TG neurons has still unclear. The present study aimed to investigate the effect of pH 7.0 on ASICs and to investigate whether the effect of CGRP can modulate ASICs activity in both the small-to-medium-sized and large-sized neurons. Primary-culture TG neurons were performed by whole-cell patch clamp recording that injected depolarizing current steps in long and short periods. The electrophysiological properties of neurons were compared between physiological pH and pH 7.0 in both with and without CGRP. After lowering pH, pH 7.0 increased the excitability in the small-to-medium-sized neurons while pH 7.0 cannot modulate the excitability in the large-sized neurons. Moreover, CGRP can directly increase the excitability in the large-sized neurons by activating its receptor. However, CGRP would modulate the excitability in the small-to-medium-sized neurons via the activation of satellite glia cells with unknown mechanism, but would possibly be the signaling cascade pathways. These finding indicate that pH 7.0 can modulate the excitability of small-to-medium-sized neurons and CGRP can directly modulate the excitability of large-sized neurons resulting in the increase of pain perception. However, the effect of CGRP to modulate the excitability in pH 7.0 should be further investigated.