Calcium-Activated K+ Channels (KCa) and Therapeutic Implications

Dudem, Srikanth; Sergeant, Gerard P.; Thornbury, Keith D.; Hollywood, Mark A.

doi:10.1007/164_2021_459

Cited by 10 publications

(14 citation statements)

References 175 publications

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“…Large-conductance calcium-and voltage-dependent potassium (BK) channels are composed of pore-forming α subunits (Slo1, KCNMA1) and auxiliary subunits, including β1 through β4 (KCNMB1 through KCNMB4), γ1 through γ4 (LRRC26, LRRC52, LRRC55, LRRC38), and LINGO1 through LINGO4 [1][2][3][4][5][6][7]. BK channels are ubiquitously distributed in the body and play vital roles in various physiological and pathological processes [8,9].…”

Section: Introductionmentioning

confidence: 99%

BK channels in microglia

Sun¹

2023

Brain Science Advances

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Large-conductance calcium-and voltage-dependent potassium (BK) channels are ubiquitously expressed in mammalian cells and participate in various physiological and pathological processes such as neurotransmission and cerebral ischemia. BK channels comprise up to four pore-forming α subunits and zero to four accessory subunits. Although microglial BK currents were initially recorded 27 years ago, their roles have long been elusive. Studies have demonstrated that BK channels modulate the activation, phagocytosis, and probably migration of microglia and have associated microglial BK channels with many neurological diseases, including neuropathic pain and stroke. This review summarizes the available information regarding the biophysical, functional, and pathological aspects of microglial BK channels and discusses future directions of research into these channels.

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Section: Introductionmentioning

confidence: 99%

BK channels in microglia

Sun¹

2023

Brain Science Advances

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“…Considering the variety of cell types in which BK channels are expressed and the functional roles they play, it is probably safe to assert that BK channels exhibit broader functional diversity than any other voltage‐dependent K + channel (Gonzalez‐Perez & Lingle, 2019; Dudem et al . 2021).…”

Section: Introductionmentioning

confidence: 99%

“…First, we summarize the initial identification and description of functional properties of subunits containing leucine rich repeat (LRR) domains that are pertinent to BK channels. Since LRRC subunits of BK channels have been included in other recent reviews (Zhang & Yan, 2014;Gonzalez-Perez & Lingle, 2019;Dudem et al 2021), here we highlight those properties of the subunits that we think are important for understanding their physiological roles and may provide clues to LRRC-dependent pathologies. Second, we summarize recent work with LRRC26 and LRRC52 that has addressed the role of LRRC proteins in native cells, with particular emphasis on what knockout (KO) of LRRC subunits may be revealing about potential pathological consequences related to the LRRC subunits.…”

Section: Introductionmentioning

confidence: 99%

“…In a given cell type, it is the intrinsic properties of a BK channel, that is, the range of V m and Ca 2+ over which a particular channel is activated, that defines the circumstances under which it functions. Considering the variety of cell types in which BK channels are expressed and the functional roles they play, it is probably safe to assert that BK channels exhibit broader functional diversity than any other voltage-dependent K + channel (Gonzalez-Perez & Lingle, 2019; Dudem et al 2021).…”

Section: Introductionmentioning

confidence: 99%

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The LRRC family of BK channel regulatory subunits: potential roles in health and disease

González-Pérez

Zhou

Ciorba

et al. 2022

The Journal of Physiology

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Large conductance K+ channels, termed BK channels, regulate a variety of cellular and physiological functions. Although universally activated by changes in voltage or [Ca2+]i, the threshold for BK channel activation varies among loci of expression, often arising from cell‐specific regulatory subunits including a family of leucine rich repeat‐containing (LRRC) γ subunits (LRRC26, LRRC52, LRRC55 and LRRC38). The ‘founding’ member of this family, LRRC26, was originally identified as a tumour suppressor in various cancers. An LRRC26 knockout (KO) mouse model recently revealed that LRRC26 is also highly expressed in secretory epithelial cells and partners with BK channels in the salivary gland and colonic goblet cells to promote sustained K+ fluxes likely essential for normal secretory function. To accomplish this, LRRC26 negatively shifts the range of BK channel activation such that channels contribute to K+ flux near typical epithelial cell resting conditions. In colon, the absence of LRRC26 increases vulnerability to colitis. LRRC26‐containing BK channels are also likely important regulators of epithelial function in other loci, including airways, female reproductive tract and mammary gland. Based on an LRRC52 KO mouse model, LRRC52 regulation of large conductance K+ channels plays a role both in sperm function and in cochlear inner hair cells. Although our understanding of LRRC‐containing BK channels remains rudimentary, KO mouse models may help define other organs in which LRRC‐containing channels support normal function. A key topic for future work concerns identification of endogenous mechanisms, whether post‐translational or via gene regulation, that may impact LRRC‐dependent pathologies.

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“…Calcium-activated K + channels (KCas) are an important subfamily of K + channels that share a common function-coupling an increase in intracellular Ca 2+ concentration to cell hyperpolarization [12,13]. KCas can be divided into three types based on conductance: big (BKCa), intermediate (IKCa) and small (SKCa) conductance calcium-activated K + channels [12,13].…”

Section: Introductionmentioning

confidence: 99%

The role of SK3 in progesterone-induced inhibition of human fallopian tubal contraction

Zhang

Zhu

Xia

et al. 2022

Reprod Biol Endocrinol

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Background Normal motor activity of the fallopian tube is critical for human reproduction, and abnormal tubal activity may lead to ectopic pregnancy (EP) or infertility. Progesterone has an inhibitory effect on tubal contraction; however, the underlying mechanisms remain unclear. Small-conductance calcium-activated K+ channel 3 (SK3) is abundantly expressed in platelet-derived growth factor receptor α positive (PDGFRα+) cells and was reported to be important for the relaxation of smooth muscle. The present study aims to explore the expression of SK3 in the human fallopian tube and its role in progesterone-induced inhibition of tubal contraction. Methods We collected specimens of fallopian tubes from patients treated by salpingectomy for EP (EP group) and other benign gynecological diseases (Non-EP group). The expression of SK3 was detected by quantitative real-time polymerase chain reaction, western blot, immunocytochemistry, and immunohistochemistry analyses. Isometric tension experiments were performed to investigate the role of SK3 in progesterone-induced inhibition of tubal contraction. Results The baseline amplitude and frequency of human fallopian tube contraction were both statistically lower in the EP group compared with the non-EP group. The expression levels of SK3 in different portions of fallopian tubes from the non-EP group were significantly higher than in those from the EP group. Progesterone had an inhibitory effect on tubal contraction, mainly on the amplitude, in both groups, and SK3 as well as other calcium-activated K+ channels may be involved. SK3-expressing PDGFRα (+) cells were detected in the human fallopian tube. Conclusions The expression of SK3 is lower in the EP group, and SK3 is involved in the progesterone-induced inhibition of human fallopian tube contraction.

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Calcium-Activated K+ Channels (KCa) and Therapeutic Implications

Cited by 10 publications

References 175 publications

BK channels in microglia

BK channels in microglia

The LRRC family of BK channel regulatory subunits: potential roles in health and disease

The role of SK3 in progesterone-induced inhibition of human fallopian tubal contraction

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