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Differential modulation of N‐type calcium channels by µ‐opioid receptors in oxytocinergic versus vasopressinergic neurohypophysial terminals
Author(s) -
OrtizMiranda Sonia I.,
Dayanithi Govindan,
VelázquezMarrero Cristina,
Custer Edward E.,
Treistman Steven N.,
Lemos José R.
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22263
Subject(s) - receptor , calcium , chemistry , opioid , modulation (music) , differential (mechanical device) , endocrinology , medicine , biophysics , biology , physics , biochemistry , acoustics , thermodynamics
Abstract Opioids modulate the electrical activity of magnocellular neurons (MCN) and inhibit neuropeptide release at their terminals in the neurohypophysis. We have previously shown that µ‐opioid receptor (MOR) activation induces a stronger inhibition of oxytocin (OT) than vasopressin (AVP) release from isolated MCN terminals. This higher sensitivity of OT release is due, at least in part, to the selective targeting of R‐type calcium channels. We now describe the underlying basis for AVP's weaker inhibition by MOR activation and provide a more complete explanation of the complicated effects on neuropeptide release. We found that N‐type calcium channels in AVP terminals are differentially modulated by MOR; enhanced at lower concentrations but increasingly inhibited at higher concentrations of agonists. On the other hand, N‐type calcium channels in OT terminals were always inhibited. The response pattern in co‐labeled terminals was analogous to that observed in AVP‐containing terminals. Changes in intracellular calcium concentration and neuropeptide release corroborated these results as they showed a similar pattern of enhancement and inhibition in AVP terminals contrasting with solely inhibitory responses in OT terminals to MOR agonists. We established that fast translocation of Ca 2+ channels to the plasma membrane was not mediating current increments and thus, changes in channel kinetic properties are most likely involved. Finally, we reveal a distinct Ca‐channel β‐subunit expression between each type of nerve endings that could explain some of the differences in responses to MOR activation. These results help advance our understanding of the complex modulatory mechanisms utilized by MORs in regulating presynaptic neuropeptide release. J. Cell. Physiol. 225: 276–288, 2010. © 2010 Wiley‐Liss, Inc.