Calcium block of Na+ channels and its effect on closing rate

Calcium ion transiently blocks Na+ channels, and it shortens the time cours e for closing of their activation gates. We examined the relation between b lock and closing kinetics by using the Na+ channels natively expressed in G H3 cells, a clonal line of rat pituitary cells, To simplify analysis, inact ivation of the Na+ channels was destroyed by including papain in the intern al medium, All divalent cations tested, and trivalent La3+, blocked a progr essively larger fraction of the channels as their concentration increased, and they accelerated the closing of the Na+ channel activation gate. For ca lcium, the most extensively studied cation, there is an approximately linea r relation between the fraction of the channels that are calcium-blocked an d the closing rate. Extrapolation of the data to very low calcium suggests that closing rate is near zero when there is no block Analysis shows that, almost with certainty, the channels can close when occupied by calcium. The analysis further suggests that the channels close preferentially or exclus ively from the calcium-blocked state.