Abstract 438: Rapid Inhibition of Pre-sympathetic Kidney-related Neurons in the Rostral Ventrolateral Medulla by Leptin

Abstract

The adipocyte-derived hormone leptin regulates satiety and plays a vital role in energy homeostasis. Several lines of evidence suggest that obesity is associated with increased prevalence of hypertension and accountable at least in part for the elevation of sympathetic nerve activity. Neurons in the rostral ventrolateral medulla (RVLM) are critical components of both the sympathetic nervous system and cardiovascular regulation. By using whole-cell patch-clamp recordings in brainstem slices we tested the hypothesis that leptin suppresses activity in pre-sympathetic kidney-related RVLM neurons. Application of leptin caused a rapid membrane hyperpolarization in 43% of recorded kidney-related RVLM neurons. Out of 14 neurons, leptin (500nM) hyperpolarized 6 neurons (from -53.3±3.5 mV to -57.0± 3.2 mV; P<0.05) and had no effects on the rest of the neurons. The input resistance was significantly increased by leptin in 6 out of 14 RVLM kidney-related neurons from 276±92 MΩ to 336±97 MΩ (P<0.05). Moreover, leptin (500nM) reduced the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) from 7.9±2.1 Hz to 5.5±2.3 Hz (P<0.05; n=5) with an average of 36% decrease without changing sEPSCs amplitude. The frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) was not affected by administration of leptin. Our study demonstrates that leptin directly hyperpolarized the kidney-related RVLM neurons and indirectly suppressed excitatory synaptic activity to pre-sympathetic kidney-related RVLM neurons. This work was supported by P30GM103337.