Melatonin Reduces Excitability in Dorsal Root Ganglia Neurons with Inflection on the Repolarization Phase of the Action Potential

Author(s)

Oliveira-Abreu, Klausen ; Silva-dos-Santos, Nathalia Maria ; Coelho-de-Souza, Andrelina Noronha ; Ferreira-da-Silva, Francisco Walber ; da Silva-Alves, Kerly Shamyra ; Cardoso-Teixeira, Ana Carolina ; Cipolla-Neto, Jose ; Leal-Cardoso, Jose Henrique

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 11, p. 13-pg., 2019-06-01.

Abstract

Melatonin is a neurohormone produced and secreted at night by pineal gland. Many effects of melatonin have already been described, for example: Activation of potassium channels in the suprachiasmatic nucleus and inhibition of excitability of a sub-population of neurons of the dorsal root ganglia (DRG). The DRG is described as a structure with several neuronal populations. One classification, based on the repolarizing phase of the action potential (AP), divides DRG neurons into two types: Without (N-0) and with (N-inf) inflection on the repolarization phase of the action potential. We have previously demonstrated that melatonin inhibits excitability in N-0 neurons, and in the present work, we aimed to investigate the melatonin effects on the other neurons (N-inf) of the DRG neuronal population. This investigation was done using sharp microelectrode technique in the current clamp mode. Melatonin (0.01-1000.0 nM) showed inhibitory activity on neuronal excitability, which can be observed by the blockade of the AP and by the increase in rheobase. However, we observed that, while some neurons were sensitive to melatonin effect on excitability (excitability melatonin sensitiveEMS), other neurons were not sensitive to melatonin effect on excitability (excitability melatonin not sensitiveEMNS). Concerning the passive electrophysiological properties of the neurons, melatonin caused a hyperpolarization of the resting membrane potential in both cell types. Regarding the input resistance (R-in), melatonin did not change this parameter in the EMS cells, but increased its values in the EMNS cells. Melatonin also altered several AP parameters in EMS cells, the most conspicuously changed was the (dV/dt)(max) of AP depolarization, which is in coherence with melatonin effects on excitability. Otherwise, in EMNS cells, melatonin (0.1-1000.0 nM) induced no alteration of (dV/dt)(max) of AP depolarization. Thus, taking these data together, and the data of previous publication on melatonin effect on N-0 neurons shows that this substance has a greater pharmacological potency on N-inf neurons. We suggest that melatonin has important physiological function related to N-inf neurons and this is likely to bear a potential relevant therapeutic use, since N-inf neurons are related to nociception. (AU)

• FAPESP's process: 14/50457-0 - Melatonin and the control of energy metabolism: basic, clinical and epidemiological research
• Grantee: José Cipolla Neto
• Support Opportunities: Research Projects - Thematic Grants