Calcium Regulation of Ion Channels

Abstract

It is well established that intracellular Ca ions modulate cellular membrane potential and thus excitability by affecting the gating of ion channels in the cell membrane. One of the targets for Ca ions are Ca²⁺ channels themselves. Certain types of voltage-gated Ca²⁺ channels exhibit Ca²⁺-dependent inactivation which limits or termintes Ca²⁺ entry into the cell during membrane depolarisation. Inactivation may not develop significantly during short depolarizations as they occur in the course of a neuronal action potential but may be of importance when the membrane is depolarized for longer time such as during a burst of action potentials. Inactivation of Ca²⁺ channels is complex and involves also voltage-dependent processes. Its nature has long been debated and is still not completely elucidated, although new insights into the mechanism of Ca²⁺-dependent inactivation came from experiments with cloned Ca²⁺ channels. In the first part of this chapter we will discuss basic features of Ca²⁺ channel inactivation and their importance for complex activity patterns. The second part of the chapter will concentrate on neuronal Ca²⁺-activated K⁺ and Cl⁻ channels. While neuronal Ca²⁺-activated K⁺ channels have been extensively studied over the last decades comparatively little is known about Ca²⁺-activated Cl⁻ channels in neurons. We will discuss the various influences of these channels on neuronal excitability. In the third part of the chapter we will review the properties of Ca²⁺-activated nonselective (CAN) cation channels in the nervous system and discuss the physiological functions that have been attributed to this channels. The maintained depolarization induced by activation of these channels is an important process that underlies a variety of physiological functions in many different types of neurons.