Frequency dependence of synaptic vesicle exocytosis in aortic baroreceptor neurons and the role of group III mGluRs.
Synaptic transmission between baroreceptor afferents and the nucleus tractus solitarius (NTS) is essential for reflex regulation of blood pressure. High frequency stimulation of the afferents in vivo leads to a decrease in synaptic strength and is generally attributed to reduction in presynaptic neurotransmitter release. It has been hypothesized that during high frequency stimulation glutamate a major neurotransmitter at the baroreceptor afferent terminals inhibits its own release via presynaptic group III metabotropic glutamate receptors (mGluRs). A key player in modulation of presynaptic release is vesicle exocytosis. The present study utilized cultured aortic baroreceptor neurons and the styryl dye FM2-10 to characterize (1) the dependence of exocytosis at these afferent nerve terminals on the frequency of neuronal activation, (2) the effect of duration of stimulation on the rate of exocytosis and (3) the role of mGluRs in the frequency-dependent modulation of exocytosis. Destaining in the FM2-10 loaded boutons during 3 min of stimulation, a measure of exocytosis, progressively decreased with increasing frequency (0.5, 1.0 and 10 Hz). Blockade of group III mGluRs with 300 microM (RS)-cyclopropyl-4-phosphonophenylglycine (CPPG) facilitated exocytosis evoked by 10 Hz stimulation but not at 0.5 Hz. The data suggest that aortic baroreceptor terminals exhibit frequency-dependent depression of exocytosis and support a role for group III mGluRs in the frequency-dependent modulation of exocytosis.
Pamidimukkala
Jaya
J
Dalton Cardiovascular Research Center, Department of Veterinary Biomedical Sciences, University of Missouri-Columbia, 134 Research Park, Rm 219, Columbia, MO 65211, USA. PamidimukkalaJ@missouri.edi
Hay
Meredith
M
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000294:innervation*; D002232:Carbocyanines / Q000378:metabolism; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008856:Microscopy, Fluorescence / Q000379:methods; D009475:Neurons, Afferent / Q000502:physiology* / Q000528:radiation effects; D011311:Pressoreceptors / Q000502:physiology* / Q000528:radiation effects; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D012397:Rosette Formation / Q000379:methods; D016704:Synapsins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013997:Time Factors
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; C086686:FM2 10; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D018094:Receptors, Metabotropic Glutamate; D016704:Synapsins; C104331:cyclopropyl-4-phosphonophenylglycine; C102718:metabotropic glutamate receptor 3; D005998:Glycine