Glucose Concentrations Influence Subfornical Organ Neuron Responsiveness to Cholecystokinin

Abstract

Cholecystokinin (CCK) is a peptide hormone released into the bloodstream by the small intestine in response to meal consumption. Although much is known about CCK's role in digestion, its effect on the central nervous system and role as a hunger suppressant are less well understood. Our lab has previously shown that circulating CCK is sensed by the subfornical organ (SFO), a circumventricular organ lacking a blood‐brain barrier, and may influence central autonomic control via activation of CCK2 receptors (Ahmed et al., 2014). The purpose of this study was to determine the effects of glucose concentration on the excitability of SFO neurons in response to CCK. SFO neurons from Sprague Dawley rats (125‐200g) were micro dissected, dissociated, and incubated at three different glucose concentrations (1mM, 5mM, and 10mM). Then, using whole‐cell and perforated patch current clamp recording techniques, the effects of bath application of CCK (10nM and 0.1nM) on membrane potential at these glucose concentrations (1mM, 5mM, and 10mM) were assessed. We found that at 1mM glucose, the majority of responding cells hyperpolarized (39% hyperpolarized [mean membrane potential (MMP): ‐14.8 ± 2.1 mV], n=13; vs. 18% depolarized [MMP: 6.4 ± 1.9 mV], n=6) in response to 0.1 nM CCK. In contrast at 5mM and 10mM glucose, CCK depolarized the majority of responding cells (53% and 40% depolarized [MMP: 10.3 ± 1.0 mV and 12.1 ± 2.7 mV], n=10 and n=10; vs. 21% and 24% hyperpolarized [MMP: ‐14.7 ± 3.9 mV and ‐11.6 ± 2.8 mV], n= 4 and n=6). This study suggests that circulating levels of glucose may affect central autonomic integration in the subfornical organ.Supported by the Canadian Institutes of Health Research