Grayanotoxin I is found in the leaves of plants belonging to the family Ericaceae (Leucothoe, Rhododendron, Andromeda, Kalmia). It binds to the sodium channel in its open state and upon binding the sodium channel gating is altered. A shift occurs in the activation of the sodium channel to the hyperpolarizing direction, leading to its persistent opening even at resting potentials (ranging from −70 to −100mV). In addition, the inactivation process of these modified sodium channels is suppressed. The resulting massive influx of Na+ ions will cause excitation followed by complete inexcitability of nerve cells. These lipid-soluble neurotoxins may modify sodium channels gating by causing immobilization of S6 segments during gating transitions and thereby during depolarization the channels ‘are freezed’ in the open state. In the guineapig atria, Grayanotoxin I produces a membrane depolarization, positive inotropic effects and arrhythmias.