Target intelligence / Profile preview

Small conductance calcium-activated potassium channel protein 3 (KCa2.3) (KCa2.3)

Target
KCa2.3
Molecular classification
Ion channel, Potassium channel, Calcium-activated potassium channel
01

Overview

The Small conductance calcium-activated potassium channel protein 3 (KCa2.3) is a voltage-independent potassium channel that is activated by submicromolar concentrations of intracellular calcium [1, 2]. It functions as a heterotetramer, often associated with calmodulin, which acts as the calcium sensor to trigger channel opening [1]. KCa2.3 is predominantly expressed in the nervous system, vascular endothelium, and the heart, where it regulates membrane potential and cellular excitability [3]. In neurons, it contributes to the afterhyperpolarization phase following an action potential, thereby controlling firing patterns [1, 5].\n\nIn the vasculature, KCa2.3 is a major driver of endothelium-dependent hyperpolarization, which promotes vasodilation and regulates blood pressure [2, 3]. Pathologically, KCa2.3 dysfunction is linked to atrial fibrillation, hypertension, and neuropsychiatric conditions, while its overexpression in certain tumors facilitates cell migration and metastasis [3, 4]. Therapeutic targeting of KCa2.3 involves small molecule modulators like SKA-31 (activator) or apamin (blocker) to manage cardiovascular and neurological disorders [2, 3].

Other names
SK3KCNN3SKCA3hSK3Small conductance calcium-activated potassium channel 3
02

Mechanism of action

KCa2.3 channels open in response to increased intracellular calcium levels, allowing potassium ions to flow out of the cell, which results in membrane hyperpolarization and a subsequent reduction in cellular excitability and calcium signaling.

03

Biological functions

Signal transductionRegulation of membrane potentialNeuronal excitabilitySmooth muscle relaxationCell migration
04

Disease associations

Cardiovascular diseaseNeurodegenerative diseaseCancerHypertensionAtrial fibrillationSchizophreniaBipolar disorder
05

Safety considerations

Cardiac conduction disturbancesNeurological side effectsOff-target effects on other SK channel subtypes
06

Interacting drugs

Apamin

6 more in the full profile.

07

Biomarkers

KCNN3 CAG repeat lengthSK3 protein expression levels

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