Calcium-activated potassium channel subunit alpha-1

Calcium-activated potassium channel subunit alpha-1 (KCa1.1), also known as BK channel or Maxi-K channel, is a protein that in humans is encoded by the KCNMA1 gene. This channel is a member of the large conductance, voltage and calcium-sensitive potassium channel family, and is integral in controlling muscle tone and neuron excitability, among other physiological processes.

Function

The KCa1.1 channel is a potassium channel that facilitates the flow of potassium ions (K+) across the cell membrane. This flow is activated by changes in the cell's membrane potential and increased intracellular calcium concentrations. The unique feature of the KCa1.1 channel is its ability to respond to both voltage and calcium ions, making it a critical component in various physiological processes including regulation of smooth muscle contraction, neuron firing, and hearing.

In smooth muscle cells, the activation of KCa1.1 channels leads to hyperpolarization of the cell membrane, which in turn causes muscle relaxation. This mechanism is vital in the regulation of vascular tone and blood pressure. In neurons, the KCa1.1 channels contribute to the shaping of action potentials and the regulation of neurotransmitter release, influencing neuronal excitability and signaling.

Structure

The KCa1.1 channel is a tetramer, consisting of four alpha subunits that form the channel pore through which potassium ions pass. Each alpha subunit has seven transmembrane domains and a large C-terminal domain, which contains the sites for calcium binding. The channel's activity is modulated by its association with auxiliary beta subunits (KCNMB), which influence its calcium sensitivity and pharmacological properties.

Clinical Significance

Mutations in the KCNMA1 gene have been associated with several medical conditions, including epilepsy, paroxysmal nonkinesigenic dyskinesia (PNKD), and hypertension. These conditions underscore the importance of the KCa1.1 channel in maintaining proper electrical signaling in muscles and neurons. Pharmacological modulation of this channel is being explored as a therapeutic strategy for diseases related to muscle tone and neuronal excitability, such as asthma, stroke, and urinary incontinence.

Research

Research on the KCa1.1 channel continues to uncover its roles in various physiological and pathological processes. Studies have shown its involvement in the regulation of endothelial cell function, suggesting a role in angiogenesis and vascular remodeling. Additionally, the channel's contribution to the control of respiratory rhythm and airway tone highlights its potential as a target for treating respiratory disorders.