KCa2

KCa2 channels, also known as small-conductance calcium-activated potassium channels (SK channels), are a family of voltage-independent potassium channels that open in response to increases in intracellular calcium. They are activated by calmodulin, which acts as the Ca2+ sensor, and assemble as homotetramers of three subtypes—SK1, SK2, and SK3—encoded by KCNN1, KCNN2, and KCNN3 genes. In some cells, heteromeric combinations among these subunits can occur, influencing channel properties and tissue distribution.

Functionally, KCa2 channels contribute to the medium afterhyperpolarization following action potentials, thereby regulating neuronal excitability, firing patterns, and synaptic integration. They are widely expressed in the central and peripheral nervous systems, with notable roles in learning, memory, and the modulation of dendritic signaling. While predominantly neuronal, SK channels are also found in certain peripheral tissues, including vascular endothelium, where they can participate in calcium-dependent hyperpolarization processes.

Pharmacologically, KCa2 channels are selectively blocked by apamin, a peptide toxin, making them a useful tool for studying SK currents. Other agents modulate SK channel activity, including UCL1684 as a blocker and NS8593 as a negative gating modulator, while positive modulators such as EBIO and CyPPA enhance channel opening. These modulators are of interest for research into neurological and cognitive disorders, as well as conditions involving abnormal neuronal excitability.

In summary, KCa2 channels are calcium-activated, calmodulin-regulated potassium channels that shape neuronal excitability and plasticity, with implications for both basic neuroscience and potential therapeutic development.