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Tachykinins modulate multiple ionic conductances in voltage-clamped rat spinal dorsal horn neurons
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TACHYKININS MODULATE MULTIPLE IONIC CONDUCTANCES IN VOLTAGE-CLAMPED RAT SPINAL DORSAL HORNNEURONS ~. RANDIC1 and K. MURASE2 Dept. Physiol. & Pharmacol., College of Veterinary Medicine, Iowa State Univ., Ames, IA, 50011, USA 2
Information & Computer Sciences, Toyohashi Univ. of Technology, Tempaku, Toyohashi 440 Japan The membrane actions of substance P (SP), and a related tachykinin, neurokinin A (NKA) have been investigated by means of a single electrode voltage-clamp technique in the immature rat dorsal horn neurones using an in v i t r o spinal cord slice preparation. When the membrane potential was held at )he resting level of between -75 to -55 mV, bath application of SP or NKA (10"" to 10-~ M, for 1 to 3 min) induced an inward s h i f t in the holding current lasting several minutes. The magnitude of this effect varied between 10 and 400 pA depending upon the concentration of the peptides and the holding potential. When a dorsal horn neurone was held at the resting level and subjected to Is depolarizing commands to membrane potentials between -60 and -35 mV, slow inward relaxations and inward t a i l currents, the l a t t e r on repolarization to the holding potential, were recorded. During the tachykinin-induced inward s h i f t in the holding current the inward relaxation and the t a i l current were augmented in a dose-related manner. The SP-induced augmentation of the slow inward relaxation and the inward tai19~urrent is l i k e l y to be due to the enhancen~nt of the persistent slow ~ current+ because the effect was present, and even augmented in a Ca~ ~ree, Ba" e~ontainiB~ solution, i t was reduced or completely abolished by Ca~ -free, Co~ - or Mg~ -containing + + solutions, and is largely independent of the ~hanges in external Na , K or Cl- ions. Moreover, in the presence of the K -channel blocker, tetraethylammonium (TEA), the effect is increased. Depolarizing voltage commands to potentials positive to -35 mV evoked a large o@~ward K current response in the dorsal horn neurones, which was in part Ca~ -sensitive. The outward current responseg~as augmen~;~d by SB; The SP effect persists, although being reduced in a Ca~--free, Ba~" or Co~-containing solutions. ^ Z+ Z+ In a Ca -free solution containing Co and TEA, the augmentation of the persistent slow Caz+ current and the out~j~rd K÷ current by SP was abolished. However, the SP-induced increase in a Ca~ -sensitive, voltage insensitive conductance remained and the response showed a reversal at about -20 mV. Thi~ current may be a result of a tachykinin-activated non-specific increase in Na" and K- permeability of the membrane of dorsal horn neurones. Effects of SP on other ionic currents present in the spinal dorsal horn neurones were also examined. The inward r e c t i f i e r current, present in most of the tested cells, was not significantly modified by SP. Although the M-like current was noticeably rare in the examined c e l l s , in cells where I M was present, SP caused only a small reduction of the current. Effects of NKA on the immature rat spinal dorsal horn neurones were phenomenologically identical to those of SP. Physiological consequences of tachykinin membrane actions on resting potential, e x c i t a b i l i t y and bursting f i r i n g pattern of dorsal horn neurones w i l l be discussed.
TACHYKININS MODULATE MULTIPLE IONIC CONDUCTANCES IN VOLTAGE-CLAMPED RAT SPINAL DORSAL HORNNEURONS ~. RANDIC1 and K. MURASE2 Dept. Physiol. & Pharmacol., College of Veterinary Medicine, Iowa State Univ., Ames, IA, 50011, USA 2
Information & Computer Sciences, Toyohashi Univ. of Technology, Tempaku, Toyohashi 440 Japan The membrane actions of substance P (SP), and a related tachykinin, neurokinin A (NKA) have been investigated by means of a single electrode voltage-clamp technique in the immature rat dorsal horn neurones using an in v i t r o spinal cord slice preparation. When the membrane potential was held at )he resting level of between -75 to -55 mV, bath application of SP or NKA (10"" to 10-~ M, for 1 to 3 min) induced an inward s h i f t in the holding current lasting several minutes. The magnitude of this effect varied between 10 and 400 pA depending upon the concentration of the peptides and the holding potential. When a dorsal horn neurone was held at the resting level and subjected to Is depolarizing commands to membrane potentials between -60 and -35 mV, slow inward relaxations and inward t a i l currents, the l a t t e r on repolarization to the holding potential, were recorded. During the tachykinin-induced inward s h i f t in the holding current the inward relaxation and the t a i l current were augmented in a dose-related manner. The SP-induced augmentation of the slow inward relaxation and the inward tai19~urrent is l i k e l y to be due to the enhancen~nt of the persistent slow ~ current+ because the effect was present, and even augmented in a Ca~ ~ree, Ba" e~ontainiB~ solution, i t was reduced or completely abolished by Ca~ -free, Co~ - or Mg~ -containing + + solutions, and is largely independent of the ~hanges in external Na , K or Cl- ions. Moreover, in the presence of the K -channel blocker, tetraethylammonium (TEA), the effect is increased. Depolarizing voltage commands to potentials positive to -35 mV evoked a large o@~ward K current response in the dorsal horn neurones, which was in part Ca~ -sensitive. The outward current responseg~as augmen~;~d by SB; The SP effect persists, although being reduced in a Ca~--free, Ba~" or Co~-containing solutions. ^ Z+ Z+ In a Ca -free solution containing Co and TEA, the augmentation of the persistent slow Caz+ current and the out~j~rd K÷ current by SP was abolished. However, the SP-induced increase in a Ca~ -sensitive, voltage insensitive conductance remained and the response showed a reversal at about -20 mV. Thi~ current may be a result of a tachykinin-activated non-specific increase in Na" and K- permeability of the membrane of dorsal horn neurones. Effects of SP on other ionic currents present in the spinal dorsal horn neurones were also examined. The inward r e c t i f i e r current, present in most of the tested cells, was not significantly modified by SP. Although the M-like current was noticeably rare in the examined c e l l s , in cells where I M was present, SP caused only a small reduction of the current. Effects of NKA on the immature rat spinal dorsal horn neurones were phenomenologically identical to those of SP. Physiological consequences of tachykinin membrane actions on resting potential, e x c i t a b i l i t y and bursting f i r i n g pattern of dorsal horn neurones w i l l be discussed.