The response of cat spinal motoneurones to the intracellular application of agents with local anaesthetic action.

QX-222 (the trimethyl analogue of lignocaine), methylxylocholine, lignocaine and pentobarbitone were iontophoresed intracellularly into cat lumbosacral motoneurones. Iontophoresis and recording was either from a triple-barrelled microelectrode unit or from two separately advanced microelectrodes. QX-222 and methylxylocholine caused a very slow reversible block of the current-evoked and antidromic action potentials (AP) with no significant change of membrane potential (EM). Lignocaine had a minimal blocking effect on the AP. No change, or only a small decrease, of membrane slope conductance (GM) was seen when the APs had been totally abolished. QX-222 and methylxylocholine reduced the massive GM increase evoked by the passage of large depolarizing currents and converted the post-current hyperpolarization (time constant 120-150 ms) into a depolarization of similar time course. It is suggested that the quaternary local anaesthetics can reduce the fast and slow voltage-dependent potassium conductances. Both agents totally blocked AP generation without decreasing the magnitude of the Ia e.p.s.p. It is suggested that intracellularly iontophoresed QX-222 (on account of its low lipid solubility) could be used as a pharmacological tool to block specifically the active Na and channels in only the cell impaled by the microelectrodes.