BK
 Ca
 -Cav Channel Complexes Mediate Rapid and Localized Ca
 2+
 -Activated K
 +
 Signaling

Berkefeld, Henrike; Sailer, Claudia A.; Bildl, Wolfgang; Rohde, V.; Thumfart, Jörg Oliver; Eble, Silke; Klugbauer, Norbert; Reisinger, Ellen; Bischofberger, Josef; Oliver, Dominik; Knaus, Hans−Günther; Schulte, Uwe; Fakler, Bernd

doi:10.1126/science.1132915

Cited by 338 publications

(288 citation statements)

References 41 publications

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“…However, this reduction may not univocally depend only on K(v) or Ks channels, because even if such channels are blocked, melatonin can still exert its effect of reducing cell proliferation/viability through a pathway involving I BK . BK channel activation requires Ca 2 þ entry which, in turn, activates BK channels located in close vicinity to the Ca 2 þ source (Berkefeld et al, 2006;Marcantoni et al, 2010). According to Berkefeld et al (2006) and Marcantoni et al (2010), our results on I BK could be explained suggesting that melatonin was able to cause the shift of BK channels far from L-type Ca 2 þ channels, leading to the impairment of BK channels assembly and functionality and thus to the reduction of I BK and its kinetics.…”

Section: Ctrmentioning

confidence: 61%

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Squecco

Tani

Zecchi‐Orlandini

et al. 2015

European Journal of Pharmacology

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Chemical compounds studied in this article:α-Dendrotoxin (PubChem SID: 135651983) Chromanol (PubChem CID: 92890) Iberiotoxin (PubChem CID: 16132435) Melatonin (PubChem CID: 896) Nifedipine (PubChem CID: 4485) a b s t r a c t Big efforts have been dedicated up to now to identify novel targets for cancer treatment. The peculiar biophysical profile and the atypical ionic channels activity shown by diverse types of human cancers suggest that ion channels may be possible targets in cancer therapy. Earlier studies have shown that melatonin exerts an oncostatic action on different tumors. In particular, it was shown that melatonin was able to inhibit growth/viability and proliferation, to reduce the invasiveness and metastatic properties of human estrogen-sensitive breast adenocarcinoma MCF-7 cell line cultured in growth medium, with substantial impairments of epidermal growth factor (EGF) and Notch-1-mediated signaling. The purpose of this work was to evaluate on MCF-7 cells the possible effects of melatonin on the biophysical features known to have a role in proliferation and differentiation, by using the patch-clamp technique. Our results show that in cells cultured in growth as well as in differentiation medium melatonin caused a hyperpolarization of resting membrane potential paralleled by significant changes of the inward Ca 2 þ currents (T-and L-type), outward delayed rectifier K þ currents and cell capacitance. All these effects are involved in MCF-7 growth and differentiation. These findings strongly suggest that melatonin, acting as a modulator of different voltage-dependent ion channels, might be considered a new promising tool for specifically disrupting cell viability and differentiation pathways in tumour cells with possible beneficial effects on cancer therapy.

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Section: Ctrmentioning

confidence: 61%

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Squecco

Tani

Zecchi‐Orlandini

et al. 2015

European Journal of Pharmacology

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“…So far, however, experimental procedures enabling unbiased and comprehensive access to the environment of membrane proteins have been missing or have just begun to evolve (17)(18)(19)(20)(21)(22)(23)34).…”

Section: Discussionmentioning

confidence: 99%

“…Antibody-based affinity purification (AP) combined with quantitative MS is a target-directed approach, which, theoretically, allows for strong enrichment of both target proteins and more stably associated partners with tight control of specificity and interaction stringency (16). In fact, AP-based proteomics were successfully used for identification of accessory subunits and regulators of various ion-channel proteins (17)(18)(19)(20)(21)(22)(23). Notwithstanding, there remain several sources of error that are aggravated considerably when approaching protein networks such as those comprising nanoenvironments.…”

mentioning

confidence: 99%

Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain

Müller

Haupt

Bildl

et al. 2010

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

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Local Ca 2+ signaling occurring within nanometers of voltage-gated Ca 2+ (Cav) channels is crucial for CNS function, yet the molecular composition of Cav channel nano-environments is largely unresolved. Here, we used a proteomic strategy combining knockoutcontrolled multiepitope affinity purifications with high-resolution quantitative MS for comprehensive analysis of the molecular nano-environments of the Cav2 channel family in the whole rodent brain. The analysis shows that Cav2 channels, composed of poreforming α1 and auxiliary β subunits, are embedded into protein networks that may be assembled from a pool of ∼200 proteins with distinct abundance, stability of assembly, and preference for the three Cav2 subtypes. The majority of these proteins have not previously been linked to Cav channels; about two-thirds are dedicated to the control of intracellular Ca 2+ concentration, including G proteincoupled receptor-mediated signaling, to activity-dependent cytoskeleton remodeling or Ca 2+ -dependent effector systems that comprise a high portion of the priming and release machinery of synaptic vesicles. The identified protein networks reflect the cellular processes that can be initiated by Cav2 channel activity and define the molecular framework for organization and operation of local Ca 2+ signaling by Cav2 channels in the brain.calcium channel | Ca 2+ signaling | proteome | biochemistry | mass spectrometry

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“…Differential sensitivity to ‘local’ and ‘global’ Ca 2+ signals has been successfully probed for Ca 2+ ‐activated K + (and some other) channels (Berkefeld et al . 2006) with two Ca 2+ buffers, EGTA and BAPTA. EGTA is a ‘slow’ Ca 2+ buffer which cannot block fast local Ca 2+ elevations while BAPTA is a ‘fast’ buffer that is able to block both local and global Ca 2+ signals (Augustine et al .…”

Section: Coupling Between Ano1 and Endoplasmic Reticulum; Is This A Gmentioning

confidence: 99%

Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals

Jin

Shah

et al. 2014

The Journal of Physiology

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Ca2+‐activated chloride channels (CaCCs) regulate numerous physiological processes including epithelial transport, smooth muscle contraction and sensory processing. Anoctamin‐1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell types, yet our understanding of the mechanisms of ANO1 activation and regulation are only beginning to emerge. Ca2+ sensitivity of ANO1 is rather low and at negative membrane potentials the channel requires several micromoles of intracellular Ca2+ for activation. However, global Ca2+ levels in cells rarely reach such levels and, therefore, there must be mechanisms that focus intracellular Ca2+ transients towards the ANO1 channels. Recent findings indeed indicate that ANO1 channels often co‐localize with sources of intracellular Ca2+ signals. Interestingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca2+ release sites of the intracellular Ca2+ stores. Such preferential coupling may represent a general mechanism of ANO1 activation in native tissues.

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BK _Ca -Cav Channel Complexes Mediate Rapid and Localized Ca ²⁺ -Activated K ⁺ Signaling

Cited by 338 publications

References 41 publications

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain

Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals

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BK Ca -Cav Channel Complexes Mediate Rapid and Localized Ca 2+ -Activated K + Signaling

Cited by 338 publications

References 41 publications

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain

Activation of Ca2+‐activated Cl− channel ANO1 by localized Ca2+ signals

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BK _Ca -Cav Channel Complexes Mediate Rapid and Localized Ca ²⁺ -Activated K ⁺ Signaling

Activation of Ca²⁺‐activated Cl⁻ channel ANO1 by localized Ca²⁺ signals