GSBS Student Publications

Title

Differential modulation of N-type calcium channels by micro-opioid receptors in oxytocinergic versus vasopressinergic neurohypophysial terminals

Student Author(s)

Cristina Velazquez-Marrero

GSBS Program

Neuroscience

UMMS Affiliation

Department of Psychiatry; Department of Physiology

Date

5-29-2010

Document Type

Article

Medical Subject Headings

Analgesics, Opioid; Animals; Arginine Vasopressin; Calcium; Calcium Channels, N-Type; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Male; Oxytocin; Patch-Clamp Techniques; Pituitary Gland, Posterior; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Synapses; Synaptic Transmission

Disciplines

Life Sciences | Medicine and Health Sciences | Neuroscience and Neurobiology

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 micro-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 beta-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.

Rights and Permissions

Citation: J Cell Physiol. 2010 Oct;225(1):276-88. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Journal of cellular physiology

PubMed ID

20509142