Helothermine

HLTx inhibits ryanodine receptors of sarcoplasmic reticulum and both calcium channels and potassium channels.^[3][4][5]

The effects of HLTx on voltage-dependent calcium channels have been tested in granule cells of the cerebellum. In these cells, HLTx inhibits up to 67% of the calcium currents, acting on multiple subtypes. This inhibition is reversible, concentration-dependent and practically voltage-independent. No effects on the activation and inactivation kinetics were observed. A small shift in the steady-state inactivation curve has been reported. IC50 is 0.25 μM.^[4]

HLTx inhibits both delayed rectifier and A-type potassium channels in cerebellar granular cells. HLTx reduces the A-type current in a voltage and concentration-dependent way, with an IC50 of 0.52 μM. It slows down both the activation and the inactivation kinetics of the A-type current. The block of the delayed-rectifier current is not voltage-dependent, but only concentration-dependent, with an IC50 of 0.83 μM.^[5]

The ryanodine receptor, both in skeletal and in cardiac sarcoplasmic reticulum (SR), is inhibited by HLTx. The affinity of the toxin is much higher for the skeletal- than for the cardiac SR receptors, but binding is reversible in both cases.^[3]

The main effect of HTLx appears to be the induction of hypothermia. Other effects caused by the toxin include lethargy, intestinal distension/diarrhea and paralysis of the rear limbs. Sporadic tonic convulsions can occur when the intoxicated animals are touched on the dorsal parts of their body.^[5] The specific toxins of the Mexican beaded lizard were probably evolved to immobilize its prey, as these lizards move very slowly.^[1]

^{[1] [2] [3] [4] [5]}