Effect of Nifedipine on Low-Threshold Voltage-Activated Ca2+Channels in Thalamic Neurons of the Rat

In neurons of the rat thalamic nucl. lateralis dorsalis, we analyzed the effect of a well-known antihypertensive agent, nifedipine, on low-threshold Ca2+ channels that, according to their kinetics of activation, were classified as fast and slow subtypes. The transmembrane currents through the respective channels in freshly isolated neurons obtained from 14- to 17-day-old rats were measured using a patch-clamp technique in the whole-cell configuration. The fast component of the Ca2+ current demonstrated a higher sensitivity to nifedipine (Amax = 81%, IC50 = 22 μM) than the slow component did (Amax = 51%, IC50 = 28 μM). Nifedipine changed the activation and inactivation characteristics of the fast and slow current components, although in a different manner. Therefore, the affinity of nifedipine for the respective channels, which determine the above components, is different and depends on the functional state of such channels. The data obtained allow us to estimate in detail the pharmacological characteristics of the channels under study and to hypothesize on the mechanisms underlying interaction between nifedipine and channels of the above subtypes.