Goniopora toxin (GPT) is a polypeptide toxin from the marine Goniopora species coral.[1] Two toxins from this source have been identified, one acting on sodium channels and one acting on calcium channels.[2][3][4]
The toxin acting on Na+ channels has a molecular weight of 12 kDa and consists of 105 amino acids. The GPT that acts on Ca2+ channels has a molecular weight of 19 kDa; its structure is as of yet unknown.
The 12 kDa GPT inhibits the inactivation of Na+ channels. This results in a maintained open state of the channel and allows for more Na+ influx.[2][5][6] As a result, the action potential duration is prolonged. The maintained open state of sodium channels induces a longer-lasting action potential, which allows for persistent activation of calcium channels and more calcium influx.[2][5] The prolongation of the action potential and its subsequent positive inotropic effect can be influenced by stimulus frequency; at higher frequencies (1 Hz), the effects of GPT were suppressed.[2] Furthermore, the effects of GPT on the sodium channels depend on the membrane potential of the cell preceding GPT binding, suggesting that the effects of GPT are potential-dependent. Also, in the presence of GPT, sodium channels are activated in response to an unusually small depolarizing stimulus.[7] The 19 kDa GPT stimulates Ca2+ influx and its activity can be prevented in the presence of a calcium channel blocker.[1][4] This suggests that GPT directly activates Ca2+ channels or indirectly activates Ca2+ by influencing sodium currents.
Frequency-dependent effects of GPT were studied on bullfrog atrial muscle.[2] Application of GPT on the muscle showed broadening of action potential duration and showed a positive inotropic effect. When the stimulus frequency was increased, the effects of GPT were considerably suppressed as opposed to low-frequency stimulation. Also, the action potential was prolonged when long intervals of stimulation (1-3 min), in the presence of GPT, were used. In addition, when the cell membrane was hyperpolarized, the effects of GPT also increased, suggesting a potential-dependent effect on GPT toxicity.
Various GPT concentrations (10 – 100 nM) were added to guinea-pig blood vessels, which induced a contraction of the thoracic aorta, portal vein, and mesenteric and femoral arteries via an action on the innervation of the vessels.[3]
In neuroblastoma cells, even a small depolarizing stimulus can cause activation of sodium channels in the presence of GPT.[8]
In the rabbit myocardium GPT enhances atrial contractility and induce arrhythmias at concentrations above 30 nM.[8] The action potential duration was irreversibly prolonged, but there was no effect on the amplitude of the action potential or an effect on the resting membrane potential.
In guinea-pig ventricular cells, the 12 kDa GPT prolonged the action potential by acting on sodium channels, again with no effect on action potential amplitude and the resting membrane potential.[9]
At a concentration of 1.7 μM, the 19 kDa GPT induced contraction of the guinea pig ileum. This contraction was inhibited by a calcium channel blocker.[4]
In cultured chick cardiac cells the 19 kDa GPT induced an activation of calcium influx.[4] The concentration that resulted in a half-maximum activation of calcium influx was 5.3 μM.
GPT is highly toxic, with a lethal dose found in mice of 0.3-0.5 mg/kg when the 12 kDa GPT was injected intraperitoneally.[6][8] Symptoms consist of hypersensitivity, paralysis of hind limbs, diarrhea, rigidity of the entire body, and GPT can lead to a blue or purple discoloration of the skin. Tetrodotoxin, a sodium channel blocker, can be administered to suppress the prolonged action potential. Ca2+-channel blockers (e.g. nitrendipine and desmethoxyverapamil) can be used to suppress the effects of the calcium channel toxin.[1][4][9]