Voltage-dependent kappa-opioid modulation of action potential waveform-elicited calcium currents in neurohypophysial terminals.
Release of neurotransmitter is activated by the influx of calcium. Inhibition of Ca(2+) channels results in less calcium influx into the terminals and presumably a reduction in transmitter release. In the neurohypophysis (NH), Ca(2+) channel kinetics, and the associated Ca(2+) influx, is primarily controlled by membrane voltage and can be modulated, in a voltage-dependent manner, by G-protein subunits interacting with voltage-gated calcium channels (VGCCs). In this series of experiments we test whether the kappa- and micro-opioid inhibition of Ca(2+) currents in NH terminals is voltage-dependent. Voltage-dependent relief of G-protein inhibition of VGCC can be achieved with either a depolarizing square pre-pulse or by action potential waveforms. Both protocols were tested in the presence and absence of opioid agonists targeting the kappa- and micro-receptors in neurohypophysial terminals. The kappa-opioid VGCC inhibition is relieved by such pre-pulses, suggesting that this receptor is involved in a voltage-dependent membrane delimited pathway. In contrast, micro-opioid inhibition of VGCC is not relieved by such pre-pulses, indicating a voltage-independent diffusible second-messenger signaling pathway. Furthermore, relief of kappa-opioid inhibition during a physiologic action potential (AP) burst stimulation indicates the possibility of activity-dependent modulation in vivo. Differences in the facilitation of Ca(2+) channels due to specific G-protein modulation during a burst of APs may contribute to the fine-tuning of Ca(2+)-dependent neuropeptide release in other CNS terminals, as well.
Velázquez-Marrero
Cristina M
CM
Department of Physiology and Program in Neuroscience, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Marrero
Héctor G
HG
Lemos
José R
JR
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D008297:Male; D018408:Patch-Clamp Techniques; D010904:Pituitary Gland, Posterior / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D015220:Calcium Channels; D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D019204:GTP-Binding Proteins; D002118:Calcium