| Abstract: | The effects of quinidine on sodium (INa) and potassium (IK) currents in the Ranvier node of frog myelinated nerve fibre was studied by means of voltage clamp technique. When applied externally quinidine (5.10(-5) M) suppresses both INa and IK. Inhibition of INa can be greatly increased by repetitive membrane depolarization. After the end of stimulation the INa value recovers slowly up to the initial level (time constant being about 30 s at 12 degrees C). Unlike repetitive stimulation a single depolarizing pulse of long (1s) duration does not enhance appreciably the quinidine block, which permits a conclusion that quinidine interacts preferently with open sodium channels. Batrachotoxin protects the channels from the blocking action of 5.10(-5) M quinidine. The outward IK is blocked by quinidine in time- and voltage-dependent manner suggesting the interaction of the drug with open potassium channels. The results are consistent with the notion that tertiary amine quinidine, like amine local anesthetics penetrates through the membrane in the neutral form and blocks open sodium and potassium channels from inside in charged (protonated) form. Quinidine and local anesthetics are supposed to share a common receptor in the inner mouth of the sodium channel. |
