Nesfatin‐1 influences the excitability of subfornical organ neurons through actions on the Ik conductance (1129.2)

Abstract

Nesfatin‐1 is produced in several brain areas involved in metabolic processes and has been implicated in the control of ingestive behaviors and cardiovascular function. In this study, we confirm the presence of mRNA for the nucleobindin‐2 gene in the subfornical organ (SFO). We used whole‐cell patch clamp recordings in current clamp configuration to investigate the influence of nesfatin‐1 on the membrane potential of dissociated SFO neurons. We found that 80.3% (49 of 61) of neurons tested showed a response to nesfatin‐1 (100 nM, 10 nM and 1 nM) with 47.5% depolarising and 32.8% hyperpolarising. We then used voltage clamp configuration to investigate the conductances through which nesfatin‐1 may act to change the membrane potential of SFO neurons. Voltage clamp ramp and step protocols revealed a nesfatin‐1 induced enhancement of the delayed rectifier potassium conductance, IK. Pharmacological blockade of this conductance using tetraethyl ammonium chloride (TEA) greatly reduced the magnitude and occurrence of the observed hyperpolarisations, which implies that nesfatin‐1 induced hyperpolarisations are mediated through IK. This study has demonstrated that nesfatin‐1 has the ability to influence the membrane potential of SFO neurons by enhancing the IK conductance, and thus has identified the SFO as a potential site at which nesfatin‐1 may act to regulate ingestive behaviour and cardiovascular control.Grant Funding Source: Canadian Institutes for Health Research