Leptin and CCK modulate complementary background conductances to depolarize cultured nodose neurons.
We have previously reported that intraceliac infusion of leptin induces a reduction of meal size that depends on intact vagal afferents. This effect of leptin is enhanced in the presence of cholecystokinin (CCK). The mechanisms by which leptin and CCK activate vagal afferent neurons are not known. In the present study, we have begun to address this question by using patch-clamp electrophysiological techniques to examine the mechanisms by which leptin and CCK activate cultured vagal afferents from adult rat nodose ganglia. We found that leptin depolarized 41 (60%) of 68 neurons. The magnitude of membrane depolarization was dependent on leptin concentration and occurred in both capsaicin-sensitive and capsaicin-insensitive neurons. We also found that a majority (16 of 22; 73%) of nodose neurons activated by leptin were also sensitive to CCK. CCK-induced depolarization was primarily associated with the increase of an inward current (11 of 12), whereas leptin induced multiple changes in background conductances through a decrease in an outward current (7 of 13), an increase in an inward current (3 of 13), or both (3 of 13). However, further isolation of background currents by recording in solutions that contained only sodium or only potassium revealed that both leptin and CCK were capable of increasing a sodium-dependent conductance or inhibiting a potassium-dependent conductance. Our results support the hypothesis that vagal afferents are a point of convergence and integration of leptin and CCK signaling for control of food intake and suggest multiple ionic mechanisms by which leptin and CCK activate vagal afferent neurons.
Peters
J H
JH
Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, College of Veterinary Medicine, Washington State University, Pullman 99164-6520, USA. petersj@vetmed.wsu.edu
Ritter
R C
RC
Simasko
S M
SM
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D002211:Capsaicin / Q000378:metabolism; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D020738:Leptin; D002766:Cholecystokinin; D002211:Capsaicin