High-conductance calcium-activated potassium channels; Structure, pharmacology, and function

Kaczorowski, Gregory J.; Knaus, Hans Guenther; Leonard, Reid J.; McManus, Owen B.; García, María L.

doi:10.1007/bf02110699

Cited by 271 publications

(226 citation statements)

References 74 publications

Supporting

Mentioning

215

Contrasting

Unclassified

Order By: Relevance

“…I K(Ca) was also blocked by ChTX, a selective inhibitor of I K(Ca) . These properties have already been described in many smooth muscle cells (for review, see Kaczorowski et al [21]). Thus we confirmed that a significant fraction of the whole cell outward current was I K(Ca) .…”

Section: Discussionmentioning

confidence: 59%

The Involvement of Calcium Mobilization in the Calcium-Activated Potassium Currents Activated by Hyposmotic Swelling in Gastric Antral Circular Myocytes of the Guinea-Pig.

Piao

Liu²,

Lin³

et al. 2001

JJP

View full text Add to dashboard Cite

The cells of vertebrates exposed to hyposmotic media, initially swell by osmotic water equilibration, but subsequently regulate their volume (regulatory volume decrease, RVD) by a loss of KCl and water (for review, see references [1][2][3]). The mechanisms of osmoregulatory K ϩ and Cl Ϫ efflux have not been completely understood. However, K ϩ and Cl Ϫ channels have been proposed to play an important role in RVD in various kinds of cells, such as those in frog urinary bladder [4], human lymphocytic cells [5], human epithelial cells [6], human platelets [7], and epithelial cells of frog skin [8].Both extracellular and intracellular [Ca 2ϩ ] are too low in animals to be useful as osmolytes. However, the Ca 2ϩ role during RVD has been recognized for many years. Many patch-clamp studies have found that the activation of volume-regulatory K ϩ channels is controlled by Ca 2ϩ (for review, see references [9,10]). Some experiments indicated that I K(Ca) was activated by an influx of Ca 2ϩ when the cell was superfused with hyposmotic solution [6,11,12]. Other experiments have shown that I K(Ca) is activated by an intracellular Ca 2ϩ signal that is released from intracellular calcium stores during RVD [13]. But the effect of hyposmotic swelling on I K(Ca) and the role of intracellular or extracellular Ca 2ϩ in gastric smooth muscle cells has not been investigated.In our previous study, we reported that the voltageoperated calcium current (I Ca ) was increased [14] and that the volume-sensitive chloride current (I Cl ) was activated by hyposmotic swelling [15] in gastric antral myocytes of the guinea-pig. In the present study, we Key words: gastric smooth muscle cell, Ca 2ϩ -activated K ϩ current, Ca 2ϩ -induced Ca 2ϩ release, swelling.Abstract: In our study of the effects of hyposmotic swelling on the Ca 2ϩ -activated potassium currents [I K(Ca) ] and its mechanism, we employed the whole-cell patch clamp technique using the gastric antral circular myocytes of the guinea-pig. Hyposmotic swelling efficiently increased I K(Ca) , and the extent of changes in I K(Ca) was sharply dependent on the osmolarity of the perfusion solutions. When the calcium-free solution (EGTA 10 M added in calcium-free solution) was superfused, I K(Ca) was not increased by the hyposmotic swelling. Gadolinium (Gd 3ϩ ) 100 nM, a blocker of the stretch-activated nonselective cation channel, blocked the activation of I K(Ca) induced by hyposmotic swelling, but nicardipine 5 M (the Ltype calcium channel blocker) did not. Heparin 3 mg/ml, a potent inhibitor of inositol triphosphate receptor (InsP 3 R), did not inhibit the response, and caffeine 1 mM (the agonist for calcium-induced calcium release [CICR]) imitated the effect of hyposmotic swelling. Ryanodine (15 M), markedly inhibited the effect. These results suggest that hyposmotic swelling activates I K(Ca) , and the activation is associated with CICR, which is triggered by extracellular calcium influx through the stretch-activated channel (SA channel).

show abstract

Section: Discussionmentioning

confidence: 59%

The Involvement of Calcium Mobilization in the Calcium-Activated Potassium Currents Activated by Hyposmotic Swelling in Gastric Antral Circular Myocytes of the Guinea-Pig.

Piao

Liu²,

Lin³

et al. 2001

JJP

View full text Add to dashboard Cite

show abstract

“…are activated in a highly synergistic manner by elevations in intracellular Ca 2ϩ (Ca i 2ϩ ) and depolarization (1,2). When activated, the efflux of K ϩ out of the cell hyperpolarizes the membrane potential, shutting down voltage-dependent Ca 2ϩ and Na ϩ channels.…”

mentioning

confidence: 99%

Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca ²⁺

Niu

Magleby

2002

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

BK channels (Slo1) are widely distributed K+ channels that control Ca2+-dependent processes and cellular excitability. Their activation by intracellular Ca2+ (Ca\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}_{i}^{2+}\end{equation*}\end{document}) is highly cooperative, with Hill coefficients of typically 2–5. To investigate the cooperativity contributed by each of the four α subunits that form the BK channel, we studied single channels comprised of mixtures of functional subunits and subunits with a mutation to disrupt a key site (Ca-bowl) required for activation by low concentrations of Ca\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}_{i}^{2+}\end{equation*}\end{document}. As the number of functional subunits increased, we found a stepwise increase in the Hill coefficient of 0.3–0.8 per functional subunit and a stepwise decrease in the Ca\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}_{i}^{2+}\end{equation*}\end{document} required for half activation (Kd). These results show directly that BK channels can open with 0, 1, 2, 3, or 4 functional Ca-bowls, and that each subunit with a functional Ca-bowl contributes a stepwise increase to both the cooperativity of activation and the apparent Ca2+ affinity. A model with 0–4 high-affinity allosteric activators and four low-affinity allosteric activators was examined. In this model, Ca2+ bindings were independent of one another and the cooperativity arose from the joint action of the allosteric activators on the open–closed equilibrium. Although this model described well the major features of the experimental data, some differences between the observed and predicted results indicated that additional factors not included in the model also contribute to the cooperativity

show abstract

“…Scorpion venoms are rich sources of fascinating neurotoxins, which bond with high affinity and specificity to various ion channels and thus widely serve as useful tools in probing the protein mapping of ion channels and clarifying the molecular mechanism involved in the signal transmission and channel gating. Some of the peptidyl scorpion toxins such as Charybdotoxin (ChTX), 1 Iberiotoxin, and Slotoxin also block the BK currents encoded by both the Slo1 ␣-subunits and the ␤-subunits but with a higher EC 50 (5,6). Those toxins have in common very poor reversibility, which makes it difficult to study the functions of BK currents, especially in current clamp experiments, even though this property is often used to identify the existence of ␤-subunits (7)(8)(9).…”

mentioning

confidence: 99%

BmP09, a “Long Chain” Scorpion Peptide Blocker of BK Channels

Yao

Chen

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

A novel "long chain" toxin BmP09 has been purified and characterized from the venom of the Chinese scorpion Buthus martensi Karsch. The toxin BmP09 is composed of 66 amino acid residues, including eight cysteines, with a mass of 7721.0 Da. Compared with the B. martensi Karsch AS-1 as a Na ؉ channel blocker (7704.8 Da), the BmP09 has an exclusive difference in sequence by an oxidative modification at the C terminus. The sulfoxide Met-66 at the C terminus brought the peptide a dramatic switch from a Na ؉ channel blocker to a K ؉ channel blocker. Upon probing the targets of the toxin BmP09 on the isolated mouse adrenal medulla chromaffin cells, where a variety of ion channels coexists, we found that the toxin BmP09 specifically blocked large conductance Ca 2؉ -and voltage-dependent K ؉ channels (BK) but not Na ؉ channels at a range of 100 nM concentration. This was further confirmed by blocking directly the BK channels encoded with mSlo1 ␣-subunits in Xenopus oocytes. The half-maximum concentration EC 50 of BmP09 was 27 nM, and the Hill coefficient was 1.8. In outside-out patches, the 100 nM BmP09 reduced ϳ70% currents of BK channels without affecting the single-channel conductance. In comparison with the "short chain" scorpion peptide toxins such as Charybdotoxin, the toxin BmP09 behaves much better in specificity and reversibility, and thus it will be a more efficient tool for studying BK channels. A three-dimensional simulation between a BmP09 toxin and an mSlo channel shows that the Lys-41 in BmP09 lies at the center of the interface and plugs into the entrance of the channel pore. The stable binding between the toxin BmP09 and the BK channel is favored by aromatic -interactions around the center.

show abstract

High-conductance calcium-activated potassium channels; Structure, pharmacology, and function

Cited by 271 publications

References 74 publications

The Involvement of Calcium Mobilization in the Calcium-Activated Potassium Currents Activated by Hyposmotic Swelling in Gastric Antral Circular Myocytes of the Guinea-Pig.

The Involvement of Calcium Mobilization in the Calcium-Activated Potassium Currents Activated by Hyposmotic Swelling in Gastric Antral Circular Myocytes of the Guinea-Pig.

Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca ²⁺

BmP09, a “Long Chain” Scorpion Peptide Blocker of BK Channels

Contact Info

Product

Resources

About

High-conductance calcium-activated potassium channels; Structure, pharmacology, and function

Cited by 271 publications

References 74 publications

The Involvement of Calcium Mobilization in the Calcium-Activated Potassium Currents Activated by Hyposmotic Swelling in Gastric Antral Circular Myocytes of the Guinea-Pig.

The Involvement of Calcium Mobilization in the Calcium-Activated Potassium Currents Activated by Hyposmotic Swelling in Gastric Antral Circular Myocytes of the Guinea-Pig.

Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca 2+

BmP09, a “Long Chain” Scorpion Peptide Blocker of BK Channels

Contact Info

Product

Resources

About

Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca ²⁺