Ca2+-Activated Potassium Channels

Álvarez, Javier Soto; García‐Sancho, Javier

doi:10.1007/978-1-4612-4500-1_10

The Red Cell Membrane 1989

DOI: 10.1007/978-1-4612-4500-1_10

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Ca2+-Activated Potassium Channels

Javier Soto Álvarez¹,

Javier García‐Sancho²

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2014

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Targeting the Small- and Intermediate-Conductance Ca<sup>2+</sup>-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface

Cui¹,

Qin

et al. 2014

Neurosignals

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The small- and intermediate-conductance Ca²⁺-activated potassium (SK/IK) channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca²⁺ sensitivity of the SK/IK channels stems from a constitutively bound Ca²⁺-binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been developed over the past decade, and recent structural studies have revealed that the binding pocket of these positive modulators is located at the interface between the channel and calmodulin. SK/IK channel positive modulators can potentiate channel activity by enhancing the coupling between Ca²⁺ sensing via calmodulin and mechanical opening of the channel. Here, we review binding pocket studies that have provided structural insight into the mechanism of action for SK/IK channel positive modulators. These studies lay the foundation for structure-based drug discovery efforts that can identify novel SK/IK channel positive modulators. © 2014 S. Karger AG, Basel

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Targeting the Small- and Intermediate-Conductance Ca<sup>2+</sup>-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface

Cui¹,

Qin

et al. 2014

Neurosignals

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Ca2+-Activated Potassium Channels

Cited by 1 publication

References 135 publications

Targeting the Small- and Intermediate-Conductance Ca<sup>2+</sup>-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface

Targeting the Small- and Intermediate-Conductance Ca<sup>2+</sup>-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface

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