Ionic mechanisms of a novel neurotoxin from the sea anemone Anthopleura sp. in rat ventricular myocytes

Abstract

Objective: To determine the ionic mechanisms of a novel neurotoxin rhk2a obtained from the sea anemone Anthopleura sp. in rat ventricular myocytes.

Methods: Whole-cell patch-clamp recording technique was used to record the sodium, calcium, and sodium-calcium exchange currents (I(Na), I(Ca, L), and I(Na-Ca), respectively) in the isolated single rat ventricular myocytes with or without rhk2a treatment.

Results: The current-voltage (I-V) relationship for whole-cell I(Na) in the non-treated and rhk2a-treated (at the dose of 1 micromol/L) myocytes showed no significant difference (P>0.05), but the time constants for inactivation (tau(h)) were significantly greater (P<0.05) for the treated cells over the entire course of the experiment, while the time constants for activation (tau(m)) exhibited no significant difference between the two cells. The inactivation curve of I(Na) of rhk2a-treated cells was similar to that of the non-treated cells, as with the I-V relationship for whole-cell L-type calcium current (I(Ca, L) and I(Na-Ca)).

Conclusions: Delayed inactivation of Na(+) channel plays an important role in the positive inotropic effect of rhk2a, possibly resulting from the alteration in Na(+) channel kinetics induced by rhk2a. rhk2a does not directly affect I(Ca, L), or I(Na-Ca).