BKCa Related Drug Discovery Products

Numerous forms of smooth muscle have the large-conductance, Ca²⁺-activated K⁺ (BKCa) channel, which indirectly reduces contractility by hyperpolarizing the membrane. BKCa channels' capacity to react to various Ca²⁺ signals and electrical activity in smooth muscle is a reflection of their distinct sensitivity to intracellular Ca²⁺ concentrations and voltage. The channel is activated by either an increase in the intracellular Ca²⁺ content or a depolarization of the cell membrane. Action potentials are transmitted by phasic smooth muscle, which depolarizes the cell membrane and raises intracellular Ca²⁺ concentrations. The membrane potential is repolarized as a result of the activation of BKCa channels. BKCa channel activity also controls the tonic smooth muscle, which has a more negative, slowly varying membrane potential.

As a pioneer in drug discovery, Creative Biolabs is confident in providing the domestic and international customers with the best possible BKCa tools while at the most competitive price:

• BKCa Assays
• Ion Channel Cell Lines
• Ion Channel Membranes
• Membrane Protein Tools

Overview of BKCa

It is now known that the BKCa channel is made up of four identical α-subunits that co-assemble around a central axis to produce a single K⁺-selective conduction pore. This conclusion is based on both structural and functional data. The BKCa α-subunit is structurally composed of seven putative transmembrane (TM)-spanning a helical segments. The pore-forming loop structure that connects TM segments S5 and S6 creates the ion conduction channel and selectivity filter. An uncommon feature for ion channels is the extracellular location of the amino terminus of each α-subunit. An evolutionary conserved G-Y-G pattern seen in K⁺-selective ion channels makes up the selectivity filter itself. In addition, the S1–S4 segments work as a voltage sensor domain (VSD) and collectively form a unique structural module in BKCa and other voltage-gated K⁺ channels. The main voltage-sensing residues in the VSD of BKCa channels appear to be 4-5 positively and negatively charged residues scattered throughout the S2-S4 helices. Additionally, compared to Kv channels, BKCa channels exhibit less voltage sensitivity. This is most likely because there are fewer positively charged residues in the BKCa VSD that are sensitive to the transmembrane voltage.

BKCa Drug Discovery

The traditional theory that Ca²⁺ sparks are the main mechanism for channel activation and dilation in all arteries faces challenges due to apparent differences in the structure and function of BKCa in VSM cells of skeletal muscle compared to cerebral vasculature. Such heterogeneity may be used to allow for variation in the localized management of vascular resistance to match local hemodynamics with metabolic needs in relation to the involvement of BKCa in the regulation of pressure-induced membrane depolarization and contraction. It will also be crucial to understand the molecular and cellular causes of tissue heterogeneity in order to use BKCa as a possible therapeutic target and to fully grasp the systemic implications of pharmacologically altering this K⁺ channel.