Introduction

Ion channels are membrane proteins that regulate the flow of specific ions in different cellular districts (Hille, 1992). The electrical signals flowing through the central and peripheral nervous systems are finely tuned by a number of different ion channels. Many of these channels have now been cloned and their activity has been characterized through various electrophysiological methods, including patch-clamp recordings. The involvement of defective ion channels in the pathophysiology of several neurological disorders had been postulated for years. Genetic linkage studies and mutation analysis have now demonstrated that a variety of inherited diseases are indeed ion channel diseases, named also ‘channelopathies’ (Ashcroft, 1999).

This chapter focuses on episodic ataxia type 1 and type 2, two inherited diseases that have been associated with genetic mutations in specific potassium and calcium channel genes.

Episodic ataxia type 1

Clinical aspects

Episodic ataxia type 1 (EA-1) is an autosomal, dominant disorder affecting both the central and peripheral nervous systems (Brunt and van Weerden, 1990). The first unambiguous description of this human neurological syndrome was reported in 1975 by Van Dyke and co-workers (Van Dyke et al., 1975). It can be classified as a rare disease, though its prevalence is unknown. The initial symptoms occur during infancy or early childhood. The hallmark of the disease is continuous myokymia (constant muscle rippling) and episodic attacks of spastic contractions of skeletal muscles, which often result in loss of balance. Attacks of ataxia are characterized by incoordination, impaired speech, and jerking movements of the head, arms, and legs. They may be brought on by fever, startle, vestibulogenic stimulation, emotional stress, exercise, or fatigue.