Endogenous adenosine inhibits CNS terminal Ca(2+) currents and exocytosis
Authors
Knott, Thomas K.Marrero, Hector G.
Fenton, Richard A.
Custer, Edward E. Jr.
Dobson, James G. Jr.
Lemos, Jose R.
UMass Chan Affiliations
Department of PhysiologyDocument Type
Journal ArticlePublication Date
2007-02-01Keywords
AdenosineAdenosine Triphosphatases
Adenosine Triphosphate
Animals
Calcium
Calcium Signaling
Enzyme Inhibitors
Exocytosis
Feedback
Feedback, Biochemical
Hypothalamus
Male
Neuropeptides
Pituitary Gland, Posterior
Presynaptic Terminals
Rats
Rats, Sprague-Dawley
Receptor, Adenosine A1
Synaptic Transmission
Molecular and Cellular Neuroscience
Neuroscience and Neurobiology
Physiology
Metadata
Show full item recordAbstract
Bursts of action potentials (APs) are crucial for the release of neurotransmitters from dense core granules. This has been most definitively shown for neuropeptide release in the hypothalamic neurohypophysial system (HNS). Why such bursts are necessary, however, is not well understood. Thus far, biophysical characterization of channels involved in depolarization-secretion coupling cannot completely explain this phenomenon at HNS terminals, so purinergic feedback mechanisms have been proposed. We have previously shown that ATP, acting via P2X receptors, potentiates release from HNS terminals, but that its metabolite adenosine, via A(1) receptors acting on transient Ca(2+) currents, inhibit neuropeptide secretion. We now show that endogenous adenosine levels are sufficient to cause tonic inhibition of transient Ca(2+) currents and of stimulated exocytosis in HNS terminals. Initial non-detectable adenosine levels in the static bath increased to 2.9 microM after 40 min. These terminals exhibit an inhibition (39%) of their transient inward Ca(2+) current in a static bath when compared to a constant perfusion stream. CPT, an A(1) adenosine receptor antagonist, greatly reduced this tonic inhibition. An ecto-ATPase antagonist, ARL-67156, similarly reduced tonic inhibition, but CPT had no further effect, suggesting that endogenous adenosine is due to breakdown of released ATP. Finally, stimulated capacitance changes were greatly enhanced (600%) by adding CPT to the static bath. Thus, endogenous adenosine functions at terminals in a negative-feedback mechanism and, therefore, could help terminate peptide release by bursts of APs initiated in HNS cell bodies. This could be a general mechanism for controlling transmitter release in these and other CNS terminals.Source
J Cell Physiol. 2007 Feb;210(2):309-14. Link to article on publisher's siteDOI
10.1002/jcp.20827Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44183PubMed ID
17096366Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/jcp.20827
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