Modulation and Functions of Neuronal Ca²⁺ Permeable Channels

Abstract

Ca²⁺ acts as an important second messenger molecule in virtually every cell type. [Ca²⁺]i is normally kept at very low levels ~10⁻⁸–10⁻⁷ M. On the other hand the Ca²⁺ concentration of the extracellular milieu is approximately 10^-3 M. Consequently there is a very large electrochemical gradient for Ca²⁺ ions across the plasma membrane of the cell. This membrane is normally very impermeable to Ca²⁺. The Ca²⁺ permeability of the plasma membrane can be rapidly increased by opening a number of ion channels. These channels may be activated by changes in membrane potential, by agonists or, in some instances, by both. In neurons Ca²⁺ has a very large number of roles to play. Among these are the control of neuronal excitability and also the triggering of neurotransmitter release. Voltage sensitive Ca²⁺ channels and receptor operated Ca²⁺ channels have been studied extensively in nerve cells both from the peripheral and central nervous systems. In this article I shall review some of the properties of these channels, how they can be regulated physiologically and some of the consequences of this regulation.