Ionic Mechanisms of Action of Neurotensin in Acutely Dissociated Neurons From the Diagonal Band of Broca of the Rat

• Published in: Journal of neurophysiology Vol. 81; no. 1; pp. 234 - 246
• Main Authors: Jassar, Balvinder S, Harris, Kim H, Ostashewski, Paula M, Jhamandas, Jack H
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01-01-1999
• Subjects: Action Potentials - drug effects; Animals; Apamin - pharmacology; Calcium - metabolism; Calcium - physiology; Calcium Channel Blockers - pharmacology; Electric Stimulation; Electrophysiology; Frontal Lobe - cytology; Frontal Lobe - drug effects; In Vitro Techniques; Male; Membrane Potentials - physiology; Neurons - drug effects; Neurotensin - pharmacology; Patch-Clamp Techniques; Potassium Channels - drug effects; Potassium Channels - physiology; Pyrazoles - pharmacology; Quinolines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Neurotensin - antagonists & inhibitors; Tetraethylammonium Compounds - pharmacology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.1999.81.1.234

Balvinder S. Jassar ,
Kim H. Harris ,
Paula M. Ostashewski , and
Jack H. Jhamandas
Department of Medicine (Neurology) and Division of Neuroscience, University of Alberta, Edmonton, Alberta T6G 2B7, Canada
Jassar, Balvinder S., Kim H. Harris, Paula M. Ostashewski, and Jack H. Jhamandas. Ionic mechanisms of action of neurotensin in acutely dissociated neurons from the diagonal band of Broca of the rat. J. Neurophysiol. 81: 234-246, 1999. Whole cell recordings were performed on acutely dissociated neurons from the horizontal limb of the diagonal band of Broca (hDBB) from rats to elucidate the ionic mechanisms of action of neurotensin. Neurotensin caused a decrease in whole cell voltage-activated outward currents and failed to elicit a response when Ca 2+ influx was blocked by changing the external solution to the one containing 0 mM Ca 2+ and 50 µM Cd 2+ , suggesting the involvement of Ca 2+ -dependent conductances. Charybdotoxin, a specific blocker of voltage-sensitive calcium-activated K + channels ( I C ), caused a decrease in outward currents comparable with that caused by blocking calcium influx and occluded the neurotensin-induced decrease in outward currents. Similarly, 50 µM tetraethylammonium ions also blocked the neurotensin response. Also neurotensin reduced whole cell barium currents ( I Ba ) and calcium currents ( I Ca ). Amiloride and -conotoxin GVIA, but not nimodipine, were able to eliminate the neurotensin-induced decrease in I Ba . Thus T- and N- but not L-type calcium channels are subject to modulation by neurotensin, and this may account for its effects on I C . The predicted changes in action potential as a result of the blockade of currents through calcium channels culminating into changes in I C were confirmed in the bridge current-clamp recordings. Specifically, neurotensin application led to depolarization of the resting membrane potential, broadening of spike and a decrease in afterhyperpolarization and accommodation. These alterations in action potential characteristics that resulted in increased firing rate and excitability of the hDBB neurons also were produced by application of charybdotoxin. Neurotensin effects on these properties were occluded   by   2 - [(1 - 7 - chloro - 4 - quinolinyl) - 5 - (2, 6 - di - methoxyphenyl) pyrazol-3-yl) carbonylamino] tricyclo (3.3.1.1.)decan-2-carboxylic acid, a nonpeptide high-affinity neurotensin receptor antagonist. Neurotensin blockade of I C , possibly through I Ca , is a potential physiological mechanism whereby this peptide may evoke alterations in the cortical arousal, sleep-wake cycle, and theta rhythm.