Electrophysiological effects of fractions isolated from the venom of Parabuthus granulatus on calcium channels in cardiac myocytes
Du Plessis, Lissinda Hester
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Scorpion toxins specific for Na+ and K+ channels, have been studied extensively but relatively little has been done on Ca2+ channel toxins. Toxins in the venom of only two South African scorpions P. transvaalicus and P. granulatus have been found to interact with Ca2+ channels. Kurtoxin isolated from the venom of P. transvaalicus inhibits the T and L-type neuronal Ca2+ channels, whereas KLI and KLII (Kurtoxin-like peptide I and II), isolated from P. granulatus, inhibits T-type Ca2+ channel activity in mouse male germ cells. In this study the effects of fractions isolated from the venom of P. granularus on Cca2+ channels in rat ventricular myocytes were investigated by means of the whole-cell patch clamp technique. Fractions of P. granulatus crude venom were isolated with Sephadex G50 columns (fraction I-IV). Fraction III (PgIII) showed a voltage dependent increase of the inward Ca2+ current and influenced the channel kinetics by shifting the voltage dependence of activation towards more hyperpolarizing membrane potentials and decreased the rate of inactivation and deactivation. The time of the current to reach peak was also delayed. PgIII was further separated by HPLC in an attempt to identify the subfraction/s responsible for the agonistic effect. Subfraction I had an agonistic effect similar to PgIII, whereas subfraction II and III, decreased the Ca2+ current. The observed agonistic effect has not been described in the literature. The identification of new peptide structures with unique functions are important in the field of toxin research. Peptides that target Ca2+ channels can be valuable tools to characterize Ca2+ channels. Ca2+ channels in the heart are implicated in a number of pathological disorders like angina, ischemia, some arrhythmias and hypertension.
- Health Sciences