The BK channel: a vital link between cellular calcium and electrical signaling

Rothberg, Brad S.

doi:10.1007/s13238-012-2076-8

Cited by 38 publications

(29 citation statements)

References 104 publications

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“…Nifedipine depolarized cells by ∼3–5 mV, and ANO1 blockers hyperpolarized cells by ∼2–4 mV. Ca 2+ entry via Cav L in SMCs has been linked to activation of large conductance Ca 2+ ‐activated K + channels (BK) in SMCs (Greenwood & Leblanc, ; Rothberg, ), including those of the GI tract (Bayguinov et al . ).…”

Section: Discussionmentioning

confidence: 99%

ANO1 in intramuscular interstitial cells of Cajal plays a key role in the generation of slow waves and tone in the internal anal sphincter

Cobine

Hannah

Zhu

et al. 2017

The Journal of Physiology

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The mechanism underlying tone generation in the internal anal sphincter (IAS) is controversial. We examined the hypothesis that tone depends upon generation of electrical slow waves (SWs) initiated in intramuscular interstitial cells of Cajal (ICC-IM) by activation of Ca -activated Cl channels (encoded by Ano1) and voltage-dependent L-type Ca channels (encoded by Cacna1c). Phasic contractions and tone in the IAS were nearly abolished by ANO1 and Cav antagonists. ANO1 antagonists also abolished SWs as well as transient depolarizations that persisted after addition of Cav antagonists. Tone development in the IAS did not require stretch of muscles, and the sensitivity of contraction to ANO1 antagonists was the same in stretched versus un-stretched muscles. ANO1 expression was examined in wildtype and Ano1 mice with immunohistochemical techniques. Dual labelling revealed that ANO1 expression could be resolved in ICC but not smooth muscle cells (SMCs) in the IAS and rectum. Ano1, Cacna1c and Kit gene expression were the same in extracts of IAS and rectum muscles. In IAS cells isolated with fluorescence-activated cell sorting, Ano1 expression was 26.5-fold greater in ICC than in SMCs while Cacna1c expression was only 2-fold greater in SMCs than in ICC. These data support a central role for ANO1 and Cav in the generation of SWs and tone in the IAS. ICC-IM are the probable cellular candidate for ANO1 currents and SW generation. We propose that ANO1 and Cav collaborate to generate SWs in ICC-IM followed by conduction to adjacent SMCs where phasic calcium entry through Cav sums to produce tone.

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Section: Discussionmentioning

confidence: 99%

ANO1 in intramuscular interstitial cells of Cajal plays a key role in the generation of slow waves and tone in the internal anal sphincter

Cobine

Hannah

Zhu

et al. 2017

The Journal of Physiology

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“…Both aldosterone-dependent and -independent mechanisms account for stimulation of distal nephron potassium secretion 2 . BK is a Ca 2+ activated potassium channel comprised of a pore forming α subunit and regulatory β subunits (β1-β4), both of which bestow Ca 2+ dependent properties to the functional channel 8, 9 . Mice with deleted α or β BK subunits demonstrate impaired adaptation to elevated potassium intake exhibiting reduced urinary K + excretion and hyperaldosteronism 7, 10 .…”

Section: Introductionmentioning

confidence: 99%

The renal TRPV4 channel is essential for adaptation to increased dietary potassium

Mamenko

Boukelmoune

Tomilin

et al. 2017

Kidney International

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To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells. This, in turn, leads to augmented TRPV4-mediated flow-dependent calcium ion responses in freshly isolated split-opened collecting ducts from mice fed the high potassium diet. Genetic TRPV4 ablation greatly diminished BK channel activity in collecting duct cells pointing to a reduced capacity to excrete potassium. Consistently, elevated potassium intake induced hyperkalemia in TRPV4 knockout mice due to deficient renal potassium excretion. Thus, regulation of TRPV4 activity in the distal nephron by dietary potassium is an indispensable component of whole body potassium balance.

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“…In addition, BK channel gating is regulated by voltage, which is sensed by charged amino acids in transmembrane segments S2, S3, and S4 (Stefani et al, 1997;Díaz et al, 1998;Ma et al, 2006;Pantazis et al, 2010). The mechanism by which BK functionally integrates these two stimuli has been described by allosteric models (McManus and Magleby, 1991;Cox et al, 1997;Rothberg andMagleby, 1998, 1999; Horrigan and Aldrich, 2002). The common feature of these models is that the individual structural modules sensing Ca 2+ (gating ring) and voltage (transmembrane voltage-sensing domain) undergo structural rearrangements between resting and activated conformations, leading to channel opening.…”

Section: The Eukaryotic Bk Channelmentioning

confidence: 99%