Diversity and novel pharmacological properties of Ca2+ channels in Drosophila brain membranes.
Binding studies as well as affinity labelling and immunoblot techniques were used to identify and characterize the receptors for Ca2+ channel blockers in Drosophila brain membranes. Despite structural analogies with mammalian receptors, Drosophila binding sites for phenylalkylamines and 1,4-dihydropyridines, unlike those described in skeletal and cardiac muscle, were found to be located on separate Ca2+ channels. Single-channel bilayer recordings from reconstituted membranes revealed the presence of eight distinct cobalt-sensitive Ba2+-conducting channels in Drosophila brain membrane preparations. In good agreement with binding studies, the most frequently observed Ca2+ channel type (Ba2+ conductance of 13 pS) was extremely sensitive to phenylalkylamines but not affected by micromolar concentrations of 1,4-dihydropyridines. Distinct 1,4-dihydropyridine-sensitive and phenylalkylamine-insensitive channels were also identified. They had unitary Ba2+ conductances of 21 and 31 pS. A detailed analysis of drug action showed that both 1,4-dihydropyridines and phenylalkylamines first increased channel open state probability before fully blocking channel activity. Other types of channels have been identified with unitary Ba2+ conductances of 9, 41, 53, 64 and 81 pS. They were insensitive to the previously described organic Ca2+ channel blockers. The Drosophila system seems to be a unique model to analyse the properties of several different types of Ca2+ channels and particularly those of channel types that are uniquely blocked by phenylalkylamines or uniquely blocked by 1,4-dihydropyridines.
Pelzer
S
S
II. Physiologisches Institut, Medizinische Fakultät, Universität des Saarlandes, Homburg/Saar, FRG.
Barhanin
J
J
Pauron
D
D
Trautwein
W
W
Lazdunski
M
M
Pelzer
D
D
D000818:Animals; D001464:Barium / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology; D004330:Drosophila / Q000378:metabolism*; D004594:Electrophysiology; D008566:Membranes / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013997:Time Factors
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011978:Receptors, Nicotinic; D001464:Barium; D003035:Cobalt