Electrophysiological investigation of transient receptor potential melastatin-2 and 8 (Trpm2 and trpm8) channels in the mice dorsal raphe nucleus serotonergic neurons

Dorsal raphe nucleus, a major component of brain serotonergic system, not only plays a regulatory role in all body physiological processes but has an important implication in the pathophysiology of anxiety and depressive disorders, a major mental health problem worldwide, as well. Besides being the main source of serotonergic innervation to forebrain, dorsal raphe nucleus (DRN) contains 70% of brain serotonergic (5-HT) neurons. We aimed to study presence and physiological implications of TRPM8 and TRPM2 channels in DRN 5HT neurons using an electrophysiological patch clamp technique. We investigated the effects of TRPM8 agonist/ antagonist, menthol and AMTB, and TRPM2 agonist/ antagonist, ADPR/ 2-APB and ACA on the passive and active properties of the DR 5-HT responsive neurons in the coronal slices of the raphe nucleus from mice (BULB/c strain) of between 13 and 17 postnatal days after their exposure to serotonin. Application of serotonin caused hyperpolarization of DR neurons by 5.21 mV (n=24, p< 0.005). The mean membrane input resistance decreased significantly (n=22, p<0.002). Menthol resulted in depolarization of the 5-HT responsive neurons by 7 mV (control: -67.23mV, menthol: -60.74mV (n=22, p< 0.005). Pretreatment of 5-HT responsive cell with AMTB resulted in partial reversal of the cell membrane potential from control mean value -69.2±2 mV to -65±3.13 mV (n=12, p<0.005). On the contrary to our expectation ACA and 2-APB resulted in depolarization of 5-HT putative cells (n=13, p<0.05, n=11, p<0.05) respectively. In conclusion, the electrophysiological data indicates the presence of TRPM8 channel in DR 5-HT responsive neurons.