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

Abstract
The effect of imperatoxin A (IpTxa) on the ryanodine receptor type 3 (RyR3) was studied. IpTxa stimulates [3H]ryanodine binding to RyR3‐containing microsomes, but this effect requires toxin concentrations higher than those required to stimulate RyR1 channels. The effect of IpTxa on RyR3 channels was observed at calcium concentrations in the range 0.1 μM to 10 mM. By contrast, RyR2 channels were not significantly affected by IpTxa in the same calcium ranges. Single channel current measurements indicated that IpTxa induced subconductance state in RyR3 channels that was similar to those observed with RyR1 and RyR2 channels. These results indicate that IpTxa is capable of inducing similar subconductance states in all three RyR isoforms, while stimulation of [3H]ryanodine binding by this toxin results in isoform‐specific responses, with RyR1 being the most sensitive channel, RyR3 displaying an intermediate response and RyR2 the least responsive ones.