Calcium and Sodium Activated Potassium Channel Assays
Calcium activated potassium channels are calcium-gated potassium channels. They are split into three subtypes: BK channels, IK channels, and SK channels. For the most part, intracellular Ca2+ activates this family of ion channels. However, some of these channels are activated by other intracellular ligands like Na+.
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Structure
Calcium activated potassium channels are made up of two different subunits, alpha and beta. The alpha subunit, which is a tetramer, is responsible for forming the pore, the voltage sensor, and the calcium sensing region. This channel subunit consists of seven transmembrane units as well as a substantial intracellular area. The beta subunit of the channel is thought to be a regulatory subunit.
Features
- BK channel
The BK channel-deficient animals had higher mean arterial pressure and vascular tone. These data suggest that BK channels are important in smooth muscle cell relaxation. Increased intracellular calcium produces contraction in any muscle cell. Increased intracellular calcium levels in smooth muscle cells induce BK channels to open, allowing potassium ions to flow out of the cell.
- IK channel
IK channels are structurally quite similar to BK channels, with the main differences being conductance and modulation mechanisms. IK channels have been linked to vascular calcification, with blockage of the channel causing a reduction in vascular calcification. The body reacts differently when certain channels are overexpressed.
- SK channel
The major and most intriguing difference between SK Channels and other types of channels is that they are not voltage sensitive. Increased intracellular calcium levels are the sole way to open these channels. They play a role in cell hyperpolarization following an action potential. These channels' calcium-activated characteristic allows them to participate in vaso-regulation, hair cell auditory tuning, and the circadian cycle.
Published Data
| Paper Title | BK channel properties correlate with neurobehavioral severity in three KCNMA1-linked channelopathy mouse models |
| Journal | eLife |
| Published | 2022 |
| Abstract | KCNMA1 creates the pore for BK K+ channels, which control the excitability of neurons and muscles. Recently, a subset of patients with debilitating paroxysmal non-kinesigenic dyskinesia, presenting with or without epilepsy, have heterozygous KCNMA1 mutations discovered through genetic testing. The significance of KCNMA1 mutations and the underlying causes of clinical heterogeneity in PNKD3 have not yet been determined. On BK channels, neurons, and mice, they assess the relative severity of three KCNMA1 patient variations. |
| Result |
Voltage and intracellular Ca2+ both activate the BK channel, which is encoded by KCNMA1. BK currents are widely distributed throughout smooth muscle and the central nervous system. To control firing rates and neurotransmission, neuronal BK channels regulate action potential repolarization and rapid afterhyperpolarizations. Significant smooth muscle, neurobehavioral, and locomotor abnormalities are present in KCNMA1 knockout mice, and these deficits are accompanied by broad changes in cellular excitability. However, KCNMA1 knockout mice do not clearly display channelopathy symptoms. Furthermore, the majority of individuals who can be identified clinically have gain-of-function rather than loss-of-function alleles for BK channel activity.
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Fig.1. Location and consequence of KCNMA1 variants in the BK K+ channel. (Park, 2022)
Reference
- Park, S. M.; et al. BK channel properties correlate with neurobehavioral severity in three KCNMA1-linked channelopathy mouse models. Elife. 2022, 11, e77953.
