Secretin depolarizes nucleus tractus solitarius neurons through activation of a nonselective cationic conductance.
The recent suggestion that secretin may be useful in treating autism and schizophrenia has begun to focus attention on the mechanisms underlying this gut-brain peptide's actions in the central nervous system (CNS). In vitro autoradiographic localization of (125)I-secretin binding sites in rat brain shows the highest binding density in the nucleus tractus solitarius (NTS). Recent evidence suggests that intravenous infusion of secretin causes fos activation in NTS, a relay station playing important roles in the central regulation of autonomic functions. In this study, whole cell patch-clamp recordings were obtained from 127 NTS neurons in rat medullary slices. The mean resting membrane potential of these neurons was -54.7 +/- 0.3 mV, the mean input resistance was 3.7 +/- 0.2 GOmega, and the action potential amplitude of these neurons was always >70 mV. Current-clamp studies showed that bath application of secretin depolarized the majority (80.8%; 42/52) of NTS neurons tested, whereas the remaining cells were either unaffected (17.3%; 9/52) or hyperpolarized (1.9%; 1/52). These depolarizing effects were maintained in the presence of 5 microM TTX and found to be concentration dependent from 10(-12) to 10(-7) M. Using voltage-clamp techniques, we also identified modulatory actions of secretin on specific ion channels. Our results demonstrate that while secretin is without effect on net whole cell potassium currents, it activates a nonselective cationic conductance (NSCC). These results show that NTS neurons are activated by secretin as a consequence of activation of a NSCC and support the emerging view that secretin can act as a neuropeptide within the CNS.
Yang
Bo
B
Dept. of Physiology, Queen's Univ., Kingston, Ontario, Canada K7L 3N6.
Goulet
Martin
M
Boismenu
Richard
R
Ferguson
Alastair V
AV
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002412:Cations / Q000378:metabolism; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012633:Secretin / Q000378:metabolism / Q000494:pharmacology*; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D002412:Cations; D007473:Ion Channels; D018377:Neurotransmitter Agents; D012633:Secretin; D011188:Potassium