Abstract 414: Intrinsic Osmosensitivity of Neurons in the Organum Vasculosum of the Lamina Termialis is Mediated by Benzamil-Sensitive Channels

Abstract

Neurons of the Organum Vasculosum of the Lamina Terminalis (OVLT) play a pivotal role in body fluid homeostasis and blood pressure regulation. Lesion of OVLT neurons severely disrupts drinking, antidiuretic hormone secretion, and sympathetic-cardiovascular responses to acute sodium loads. Importantly, OVLT lesions also lower blood pressure in several models of salt-sensitive hypertension. Similarly, intracerebroventricular administration of the non-voltage dependent channel blocker benzamil attenuates sympathetic-cardiovascular responses to acute sodium loads and salt-sensitive hypertension. Therefore, the purpose of the present study was two-fold: 1) to establish OVLT neurons are sensitive to physiological changes in osmolality, and 2) to identify whether benzamil-sensitive channels mediate the osmosensitivity of OVLT neurons. Whole-cell patch-clamp recordings were performed in OVLT neuronal slices of male Sprague-Dawley rats (250-350g). 71% (17/24) of OVLT neurons responded to increased bath osmolality by addition of mannitol (5-20 mOsm/L). There were no differences in basic electrophysiological properties (ie, input resistance, membrane capacitance, etc) between responsive and non-responsive neurons. Increases in bath osmoality produced dose-dependent decreases in membrane potential (5 mOsm: 5.0±0.63 mV, 10 mOsm: 6.1±1.24 mV, 15 mOsm: 12.4±2.1; n=5, P<0.05) and increases in firing rates (5 mOsm: 208±32%, 10 mOsm: 246±55%, 15 mOsm: 274±101%, 20 mOsm: 496±53%; n=5, P<0.05). Bath application of benzamil (0.5 uM) significantly attenuated the membrane depolarization (0.2±0.7 vs 5.3±0.4 mV) and increased firing rate (98±6% vs 219±20%) during a 10mOsm/L increase in bath osmolality. These findings suggest OVLT neurons are sensitive to physiological changes in osmolality, and the intrinsic sensitivity of OVLT neurons are mediated by benzamil-sensitive channels.