Imperatoxin A (IpTx(a)) from Pandinus imperator stimulates [H-3]ryanodine binding to RyR3 channels

The effect of imperatoxin A (IpTx(a)) on the ryanodine receptor type 3 (RyR 3) was studied. IpTx(a) stimulates [H-3]ryanodine binding to RyR3-containin g microsomes, but this effect requires toxin concentrations higher than tho se required to stimulate RyR1 channels. The effect of IpTx(a) on RyR3 chann els was observed at calcium concentrations in the range 0.1 muM to 10 mM. B y contrast, RyR2 channels were not significantly affected by IpTx(a) in the same calcium ranges. Single channel current measurements indicated that Ip Tx(a) induced subconductance state in RyR3 channels that was similar to tho se observed with RyR1 and RyR2 channels. These results indicate that IpTx(a ) is capable of inducing similar subconductance states in all three RyR iso forms, while stimulation of [H-3]ryanodine binding by this toxin results in isoform-specific responses, with RyR1 being the most sensitive channel, Ry R3 displaying an intermediate response and RyR2 the least responsive ones. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.