title: Dynorphin exerts both postsynaptic and presynaptic effects in the Globus pallidus of the rat.
abstract: The opioids contained in striato-pallidal axons are thought to play a significant role in motor control. We examined post- and presynaptic effects of the kappa (kappa)-receptor agonist dynorphin A (1-13) (DYN13) on the globus pallidus (GP) neurons in rat brain slice preparations using the whole cell recording method. DYN13 hyperpolarized and decreased the input resistance of approximately one-quarter of neurons examined. All of these DYN13-sensitive neurons had medium-sized somata, large aspiny dendrites and generated repetitive firing without strong accommodation. The hyperpolarization was blocked by barium and was independent of TTX and intracellular chloride levels. The hyperpolarization was also selectively blocked by the kappa-antagonist nor-binaltorphimine dihydrochloride but not by the mu- or delta-antagonists. These data suggested that DYN13 activates barium-sensitive potassium currents in some GP neurons. Low- and high-intensity stimulation of the neostriatum (Str) evoked long- and short-latency GABAergic responses, respectively. Previous data suggested that the long- and the short-latency responses were due to activation of the striato-pallidal axons and the local collaterals of pallido-striatal axons, respectively. DYN13 diminished the amplitude of both the short- and long-latency GABAergic responses in all the neurons tested. The effects of DYN13 on GABAergic postsynaptic responses were also selectively blocked by a kappa-antagonist. To investigate whether the effects were pre- or postsynaptic, the effects of DYN13 on spontaneous inhibitory postsynaptic potentials (IPSPs) and TTX-independent miniature-inhibitory postsynaptic currents (IPSCs) were examined. DYN13 decreased the frequency, but not the amplitude, of spontaneous IPSCs and calcium-dependent miniature-IPSCs. However, DYN13 did not alter the cadmium-insensitive miniature-IPSCs. These results suggested that DYN13 suppressed GABA release from presynaptic terminals. This possibility was tested using a paired-stimulation test. DYN13 reduced the probability of evoking IPSCs to the first stimulation and greatly increased the success probability to the second stimulus. The amplitude of successfully evoked IPSCs was not changed with DYN13. DYN13 did not affect the excitatory postsynaptic potentials (EPSPs) or the response to iontophoretically applied GABA and glutamate. Together, these results suggest that DYN released from striato-pallidal axons controls the activity of GP neurons 1) by directly hyperpolarizing a population of neurons and 2) by presynaptically inhibiting GABA release from striato-pallidal and intrapallidal terminals.
authors.affiliation: Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Memphis, Memphis, Tennessee 38163, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ogura
authors.forename: H
authors.initials: H
authors.lastname: Kita
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D004399:Dynorphins / Q000494:pharmacology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects*; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017661:Receptors, Presynaptic / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017661:Receptors, Presynaptic; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004399:Dynorphins; D002118:Calcium