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μ‐Opioid receptor activation inhibits N‐ and P‐type Ca 2+ channel currents in magnocellular neurones of the rat supraoptic nucleus
Author(s) -
Soldo Brandi L.,
Moises Hylan C.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.787ba.x
Subject(s) - damgo , chemistry , opioid receptor , opioid , μ opioid receptor , agonist , medicine , supraoptic nucleus , biophysics , enkephalin , endocrinology , receptor , biology , biochemistry , oxytocin
1 The whole‐cell voltage‐clamp technique was used to examine opioid regulation of Ba 2+ currents ( I Ba ) through voltage‐sensitive Ca 2+ channels in isolated magnocellular supraoptic neurones (MNCs). The effects of local application of μ‐, δ‐ or κ‐opioid receptor selective agonists were examined on specific components of high voltage‐activated (HVA) I Ba , pharmacologically isolated by use of Ca 2+ channel‐subtype selective antagonists. 2 The μ‐opioid receptor selective agonist, DAMGO, suppressed HVA I Ba (in 64/71 neurones) in a naloxone‐reversible and concentration‐dependent manner (EC 50 = 170 n m , E max = 19.5 % ). The DAMGO‐induced inhibition was rapid in onset, associated with kinetic slowing and voltage dependent, being reversed by strong depolarizing prepulses. Low‐voltage activated (LVA) I Ba was not modulated by DAMGO. 3 Administration of κ‐ (U69 593) or δ‐selective (DPDPE) opioid receptor agonists did not affect I Ba . However, immunostaining of permeabilized MNCs with an antibody specific for κ 1 ‐opioid receptors revealed the presence of this opioid receptor subtype in a large number of isolated somata. 3 μ‐Opioid‐induced inhibition in I Ba was largely abolished after blockade of N‐type and P‐type channel currents by ω‐conotoxin GVIA (1 μ m ) and ω‐agatoxin IVA (100 n m ), respectively. Quantitation of antagonist effects on DAMGO‐induced reductions in I Ba revealed that N‐ and P‐type channels contributed roughly equally to the μ‐opioid sensitive portion of total I Ba . 4 These results indicate that μ‐opioid receptors are negatively coupled to N‐ and P‐type Ca 2+ channels in the somatodendritic regions of MNCs, possibly via a membrane‐delimited G‐protein‐dependent pathway. They also support a scheme in which opioids may act in part to modulate cellular activity and regulate neurosecretory function by their direct action on the neuroendocrine neurones of the hypothalamic supraoptic neucleus.