KCNA1

KCNA1 is a gene that encodes the voltage-gated potassium channel subunit alpha-1, also known as Kv1.1. It is a member of the Shaker-related Kv1 family and forms functional tetrameric potassium channels that regulate neuronal excitability. The Kv1.1 channels contribute to delayed rectifier potassium currents that help repolarize action potentials and limit repetitive firing, thereby shaping neuronal signaling and neurotransmitter release.

Expression of KCNA1 is widespread in the central nervous system, with notable presence in regions important for motor control such as the cerebellum and brainstem, and in myelinated peripheral nerves where Kv1.1 channels localize to axons and juxtaparanodal regions. By restricting excitability at presynaptic terminals and along axons, Kv1.1 channels help dampen excessive neuronal activity.

Pathogenic variants in KCNA1 cause episodic ataxia type 1 (EA1), an autosomal dominant disorder characterized by recurrent attacks of ataxia, tremor, dystonia, and myokymia. Onset typically occurs in childhood or adolescence, and attacks can last from seconds to minutes. Some individuals have a persistent, mild gait instability between episodes. Most disease-causing mutations reduce Kv1.1 channel function, exerting a dominant-negative or haploinsufficient effect that increases neuronal excitability in affected circuits.

Management of EA1 is symptomatic, with acetazolamide providing relief for some patients; 4-aminopyridine has been tried in select cases with variable response. KCNA1-related disorders illustrate the critical role of Kv1.1 channels in maintaining motor coordination and controlling neuronal excitability.