Depression of cardiac L-type calcium current by a scorpion venom fraction M1 following muscarinic receptors interaction involving adenylate cyclase pathway.
The effects of a non-toxic fraction, called M1, from Buthus occitanus tunetanus (Bot) scorpion were studied on rat cardiac contraction and calcium transient and current. A decrease in both rate and tension on isolated intact hearts as well as in calcium transient induced by depolarizing 100 K(+) solution on isolated ventricular cardiomyocytes was firstly observed. Studies with the whole cell patch clamp method showed that M1 decreased the L-type calcium current (ICa(L)) in a dose-dependent manner with an IC50 of 0.36 microg/mL and a Hill coefficient of 0.95. This effect was blocked and reversed by the specific muscarinic receptors antagonist atropine, 1 microM, and was completely prevented when cardiomyocytes were pretreated with Pertussis toxin, 1 microg/mL, to block the alpha subunit of the PTX-sensitive G proteins. These results show that M1 fraction of Bot inhibits basal calcium current by interacting with muscarinic receptors and suggest that this inhibition could be attributed to inhibition of adenylate cyclase activity by a mechanism involving PTX-sensitive G proteins.
Cheikh
Amani
A
Laboratoire Venins et Toxines, Institut Pasteur de Tunis, BP 74-1002, Tunis, Tunisia.
Benkhalifa
Rym
R
Bescond
Jocelyn
J
El Ayeb
Mohamed
M
Raymond
Guy
G
Cognard
Christian
C
Potreau
Daniel
D
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000633:toxicity*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D000242:Cyclic AMP / Q000096:biosynthesis; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors*; D012604:Scorpion Venoms / Q000633:toxicity*
D000067956:Adenylyl Cyclase Inhibitors; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D043585:Receptor, Muscarinic M2; D012604:Scorpion Venoms; D000242:Cyclic AMP; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium