The Journal of Neurophysiology Vol. 81 No. 1 January 1999, pp. 234-246
Copyright ©1999 The American Physiological Society

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

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 Ca²⁺ influx was blocked by changing the external solution to the one containing 0 mM Ca²⁺ and 50 µM Cd²⁺, suggesting the involvement of Ca²⁺-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.

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