Calcium uptake in brain synaptosomes: a pharmacologic study

Thesis/Dissertation · Wed Jan 01 00:00:00 EST 1986

OSTI ID:5509467

Rampe, D E

Pinched-off nerve endings (synaptosomes) from rat and guinea pig brain were used as a model to study Ca/sup 2 +/ entry mechanisms in neuronal tissue. Synaptosomes contain high affinity binding sites for both, 1,4-dihydropyridine Ca/sup 2 +/ channel antagonists, and activators. The thermodynamic characteristics of (/sup 3/H)nitrendipine building in synaptosomes were similar to those seen in both cardiac and smooth muscle preparations. Synaptosomes display two distinct K/sup +/-induced Ca/sup 2 +/ entry mechanisms. These are kinetically distinct with the faster of the two terminating in approx. 1 second while the slower persists for approx. minute. The slow phase uptake process is abolished in Na/sup +/-free media, is sensitive to antagonism by 3,4-dichlorobenzamil and displays a more rapid ontogenic appearance relative to the fast phase. It is likely that the slow phase represents Ca/sup 2 +/ entry via Na/sup +//Ca/sup 2 +/ exchange. The rapid inactivation of the fast phase coupled with its voltage dependence suggest that it represents Ca/sup 2 +/ entry via one or more types of voltage dependent Ca/sup 2 +/ channels. These channels may not be dihydropyridin sensitive since neither nitrendipine nor Bay K 8644 were shown to modulate synaptosomal Ca/sup 2 +/ uptake. The benzodiazepine receptor ligands Ro 5-4864, PK 11195 and diazepam all selectively inhibited fast phase Ca/sup 2 +/ entry relative to slow phase entry. In addition, these compounds altered (/sup 3/H)nitrendipine binding affinity. It is concluded that certain benzodiazepine receptor ligands can interact specifically with voltage dependent Ca/sup 2 +/ channels.

• Research Organization: State Univ. of New York, Buffalo (USA)
• OSTI ID: 5509467
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CALCIUM
MEMBRANE TRANSPORT
NERVES
PHYSIOLOGY
TRITIUM COMPOUNDS
BRAIN
CATIONS
GUINEA PIGS
LIGANDS
PHARMACOLOGY
RATS
RECEPTORS
ALKALINE EARTH METALS
ANIMALS
BODY
CENTRAL NERVOUS SYSTEM
CHARGED PARTICLES
ELEMENTS
IONS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
METALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RODENTS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques