LIDOCAINE ACCESSIBILITY TO THE OPEN STATE OF BRAIN NA+ CHANNELS INCREASES DURING DEVELOPMENT

During postnatal brain development, the function of Na+ channels under goes changes. We investigated at the single channel level whether the lidocaine sensitivity of the open state of brain Na+ channels changed during development and the underlying kinetic differences of the lidoc aine-induced open channel block between brain and muscle Na+ channels. The lidocaine affinity for the open channel state was found to be abo ut 30% higher in 15 day old than in newborn channels and reflected a h igher binding rate constant in 15 day old channels. When compared with reported values from adult muscle Na+ channels, lidocaine blocked the open state of brain channels with about ten times higher potency and reflected a lower unbinding rate constant in brain channels. These res ults indicate that the conformations of tile channel structures defini ng the lidocaine accessibility to its binding site must undergo change s during brain development and that the conformations of the channel s tructures interacting with lidocaine must be different in brain and mu scle channels.