BKCa Channel

Big-conductance Ca2+ sensitive K+ (BKca) channels are activated by calcium surge and membrane depolarization. BKCa channels are specifically blocked by iberiotoxin and less selectively by charybdotoxin. BKCa channels are composed of pore-forming a and auxiliary (3 subunits. Both BKCa,a andBKca, 3 subunits as well as their efficient coupling in the heteromultimeiic formation of BKca channel complexes are important for the function of BKCa channels. 

In addition to intracellular heme-containing proteins, big-conductance calcium-dependent K+ (BKCa) channels and calcium-spark activated transient Kca channels in plasma membrane are also tar geted by CO [3]. As well known, nitric oxide (NO) also activates BKca channels in vascular smooth muscle cells. While both NO and CO open BKCa channels, CO mainly acts on alpha subunit of BKCa channels and NO mainly acts on beta subunit of BKca channels in vascular smooth muscle cells. Rather than a redundant machinery, CO and NO provide a coordinated regulation of BKca channel function by acting on different subunits of the same protein complex. Furthermore, pretreatment of vascular smooth muscle... 

This subfamily including the large- (BKCa), intermediate-(IKca), and small-conductance (SKCa) Ca2+-activated K + channels are activated by increases in intracellular free Ca2+ concentration. The opening of DCca and SKCa channels are less voltage-dependent, whereas the activation of BKCa channel has steep voltage sensitivity. 

BKCa The diversity of BKCa channels can be attributed to the assembly of pore-forming a subunit together with four different auxiliary subunits ((31 -(34). BMS-204352 has been identified as a BKCa channel opener for the treatment of acute ischemic stroke although it has also been shown as an M-channel activator. Therapeutic applications for channel openers include epilepsy, bladder overactivity, asthma, hypertension, and psychosis. Other known BKCa channel openers include NS-8, NS-1619, NS-4, and certain aminoazaindole analogs. 

Herrera GM, Heppner TJ, Nelson MT 2001 Voltage dependence of the coupling of Ca2+ sparks to BKCa channels in urinary bladder smooth muscle. Am J Physiol Cell Physiol 280 ... 

Garcha RS, Hughes AD CNP, but not ANP or BNP, relax human isolated subcutaneous resistance arteries by an action involving cyclic GMP and BKCa channels. J Renin Angiotensin Aldosterone Syst 2006 7 87. [PMID 17083062]... 

Saponara S, Testai L, Iozzi D, Martinotti E, Martelli A, Chericoni S, Sgaragli G, Fusi F, Calderone V. 2006. ( + /-)-Naringenin as large conductance Ca(2 + )-activated K + (BKCa) channel opener in vascular smooth muscle cells. Br J Pharmacol 149 1013-1021. 

Yuan C, O Connell RJ, Jacob RE, Mason RP, Treistman SN. Regulation of the gating of BKCa channel by Upid bilayer thickness. J. Biol. Chem. 2007 282 7276-7286. 

Keef KD. Cyclic GMP-dependent protein kinase activates cloned BKCa channels expressed in mammalian cells by direct phosphorylation at serine 1072. J. Biol. Chem. 1999 274 10927-10935. 42. 

Natrin, a protein toxin (M 25 kDa) isolated from Naja atra venom belonging to the cysteine-rich secretory proteins (CRISP). It can induce a further contractile response in the endothelium-denuded thoracic aorta of mouse which has been contracted by a high-K+ solution. Furthermore, natrin can block the high-conductance Ca +-activated potassium (BKca) channel in a concentration-dependent manner [J. Wang et al, Biochemistry 2005, 44, 10145]. 

Another Kca that may modulate airway afferent nerve excitability is the large conductance Ca +-activated channel (BKca). An opener of this channel, NS 1619, inhibited citric acid induced cough in conscious guinea pigs and inhibited the generation of action potentials in guinea-pig fracheal A5 and C fibers in vifro (Fox et al. 1997). The effects of NS 1619 on A8 and C fibers were prevented by iberi-otoxin, a BKca channel-selective blocker. 

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