Opioids decrease high-voltage activated calcium currents in acutely dissociated neostriatal neurons.

A Stefani; D J Surmeier; G Bernardi

doi:10.1016/0006-8993(94)90940-7

Home/Archive/PubMed

PubMed · 8032898

Opioids decrease high-voltage activated calcium currents in acutely dissociated neostriatal neurons.

A Stefani·D J Surmeier·G Bernardi

View original source ↗Export metadata ↓

Abstract

Although the distribution of opioid receptors is central to the patch-matrix model of neostriatal organization, it has been unclear whether these receptors are located post-synaptically. Moreover, it has not yet been clarified whether opioid receptor activation in neostriatum results in the modulation of calcium and/or potassium conductances. To test this, neostriatal neurons were acutely isolated and their sensitivity to opioid receptor agonists determined. At nanomolar concentrations, both the mu-agonist [D-Ala2, MePhe4,Gly-ol5]-enkephalin (DAMGO) and the delta-agonist [D-Pen2, D-Pen5]-enkephalin (DPEPE) reversibly decreased whole-cell calcium currents in medium-sized neurons. These effects were blocked by the opiate antagonist naloxone. These findings argue that activation of post-synaptic, opioid receptors is capable of modulating the excitability of neostriatal neurons.

Explore related subjects

Calcium Channels Enkephalin, Ala(2)-MePhe(4)-Gly(5)-Enkephalin, D-Penicillamine (2,5)-Enkephalins In Vitro Techniques Neostriatum Neurons Receptors, Opioid, delta Receptors, Opioid, mu Journal Article Research Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

A Stefani, D J Surmeier, G Bernardi. 1994-04-11. Opioids decrease high-voltage activated calcium currents in acutely dissociated neostriatal neurons.. https://doi.org/10.1016/0006-8993(94)90940-7

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1996

Degradation of inositol 1,4,5-trisphosphate receptors during cell stimulation is a specific process mediated by cysteine protease activity.

Inositol 1,4,5-trisphosphate (InsP3) receptors are down-regulated in response to chronic activation of certain cell surface receptors because their degradation is accelerated. Studies on the nature of the down-regulatory process and the protease(s) responsible for receptor degradation are described here. InsP3 receptor down-regulation was not accompanied by parallel changes in the concentrations of several other relevant proteins (endoplasmic reticulum Ca2+-ATPase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and protein kinases alpha and epsilon). Thus, the down-regulatory process selectively targets InsP3 receptors for degradation. Furthermore, down-regulation was unaffected by brefeldin A and NH4Cl, indicating that InsP3 receptor degradation occurs without removal of receptors from the endoplasmic reticulum and independently of functional lysosomes. Analysis of InsP3 receptor immunofluorescence confirmed that the receptors are not redistributed prior to or during down-regulation. Finally, of a range of protease inhibitors tested, only N-acetyl-Leu-Leu-norleucinal blocked down-regulation. Thus, cysteine protease activity accounts for InsP3 receptor degradation and analysis of proteolysis in permeabilized cells indicates that this activity is calpain. Thus, InsP3 receptor down-regulation appears to result from the highly selective calpain-mediated degradation of InsP3 receptors. Calpain activity may be stimulated by the high concentrations of Ca2+ that are thought to be found in the vicinity of activated InsP3 receptors.

Calcium Channels↗

PubMed1996

Kinetic analysis of inositol trisphosphate binding to pure inositol trisphosphate receptors using scintillation proximity assay.

Inositol 1,4,5-triphosphate (InsP3) receptors are regulated by many intracellular signals including proteins and small messengers. By linking purified cerebellar InsP3 receptors to scintillation proximity assay beads, binding of radioligands can be measured without separation of bound from free ligand. InsP3 receptors assayed by scintillation proximity assay bound heparin with high affinity and stereoselectively bound InsP3 with similar affinity to cerebellar membranes. By rapidly freezing scintillation proximity assay reactions and then counting the frozen samples, both fast and slow components of [3H] InsP3 association and dissociation were identified. Our novel freeze-quench method in combination with conventional stopped-quench equipment and scintillation proximity assay allows the rapid kinetics of the interactions of pure receptors with their ligands to be resolved.

Calcium Channels↗

PubMed1996

Membrane stiffness and channel function.

Alterations in the stiffness of lipid bilayers are likely to constitute a general mechanism for modulation of membrane protein function. Gramicidin channels can be used as molecular force transducers to measure such changes in bilayer stiffness. As an application, we show that N-type calcium channel inactivation is shifted reversibly toward negative potentials by synthetic detergents that decrease bilayer stiffness. Cholesterol, which increases bilayer stiffness, shifts channel inactivation toward positive potentials. The voltage activation of the calcium channels is unaffected by the changes in stiffness. Changes in bilayer stiffness can be predicted from the molecular shapes of membrane-active compounds, which suggests a basis for the pharmacological effects of such compounds.

Calcium Channels↗