Male infertility in mice lacking the store-operated Ca2+ channel Orai1

Davis, Felicity M.; Goulding, Eugenia H.; D’Agostin, Diane M.; Janardhan, Kyathanahalli S.; Cummings, Connie A.; Bird, Gary S.; Eddy, Edward M.; Putney, James W.

doi:10.1016/j.ceca.2016.02.007

Cited by 22 publications

(13 citation statements)

References 35 publications

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“…Previous evidence showed that in MDCK cells the dominant Ca 2+ entry pathway is the store-operated Ca 2+ channels (6,10). This study shows that protriptylineevoked [Ca 2+ ] i rises were inhibited by 20% by econazole, nifedipine, and SKF96365.…”

Section: Discussionsupporting

confidence: 58%

“…Inositol 1,4,5-trisphosphate (IP 3 ), derived from activation of phospholipase C (PLC), is a predominant messenger for releasing store Ca 2+ from the endoplasmic reticulum (3,9). Mobilization of store Ca 2+ may activate Ca 2+ influx across the plasma membrane via store-operated Ca 2+ entry (10). However, uncontrolled [Ca 2+ ] i rises may induce ion movement, dysfunction of enzymes, apoptosis, and proliferation, etc.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Protriptyline on [Ca^(2+)]i and Viability in MDCK Renal Tubular Cells

et al. 2017

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Protriptyline has been used as an antidepressant. Clinically it has been prescribed in the auxiliary treatment of cancer patients. However, its effect on Ca²⁺ signaling and related physiology is unknown in renal cells. This study examined the effect of protriptyline on cytosolic free Ca²⁺ concentrations ([Ca²⁺]i) and viability in Madin-Darby canine kidney (MDCK) tubular cells. Protriptyline induced [Ca²⁺]i rises concentration-dependently. The response was reduced by 20% by removing extracellular Ca²⁺. Protriptyline-induced Ca²⁺ entry was not altered by protein kinase C (PKC) activity but was inhibited by 20% by three modulators of store-operated Ca²⁺ channels: nifedipine, econazole and SKF96365. In Ca²⁺-free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor 2,5- di-tert-butylhydroquinone (BHQ) or thapsigargin partially inhibited protriptyline-evoked [Ca²⁺]i rises. Conversely, treatment with protriptyline inhibited partially BHQ or thapsigargin-evoked [Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122 did not change protriptyline-induced [Ca²⁺]i rises. Protriptyline at 5-200 μM decreased cell viability, which was not reversed by pretreatment with the Ca²⁺ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid-acetoxymethyl ester (BAPTA/ AM). Together, in MDCK cells, protriptyline induced [Ca²⁺]i rises by evoking PLC-independent Ca²⁺ release from the endoplasmic reticulum and other unknown stores, and Ca²⁺ entry via PKCinsensitive store-operated Ca²⁺ entry. Protriptyline also caused Ca²⁺-independent cell death.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Effect of Protriptyline on [Ca^(2+)]i and Viability in MDCK Renal Tubular Cells

et al. 2017

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“…Two Ca 2+ channels regulate male fertility: (1) the Orail channel, which regulate store-operated calcium entry [ 18 ], and (2) the Catsper channel, which is the most extensively studied Ca 2+ channels in mammalian sperm [ 8 , 11 ]. The sperm-specific Catsper channel controls the intracellular Ca 2+ concentration ([Ca 2+ ]i).…”

Section: Catsper Regulation and [Ca 2+ ] Signalingmentioning

confidence: 99%

The Catsper channel and its roles in male fertility: a systematic review

Sun

Zhu

Wang

et al. 2017

Reprod Biol Endocrinol

116

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The Catsper channel is a sperm-specific, Ca2+-permeable, pH-dependent, and low voltage-dependent channel that is essential for the hyperactivity of sperm flagellum, chemotaxis towards the egg, capacitation and acrosome reaction. All of these physiological events require calcium entry into sperm cells. Remarkably, Catsper genes are exclusively expressed in the testis during spermatogenesis, and are sensitive to ion channel-induced pH change, such as NHEs, Ca2+ATPase, K+ channel, Hv1 channel and HCO3 − transporters. Furthermore, the Catsper channel is regulated by some physiological stimulants, such as progesterone, cyclic nucleotides (e.g., cAMP, cGMP), zona pellucida (ZP) glycoproteins and bovine serum albumin (BSA). All of these factors normally stimulate Ca2+ entry into sperm through the Catsper channel. In addition, the Catsper channel may be a potential target for male infertility treatment or contraception. This review will focus on the structure, functions, regulation mechanisms and medicinal targets of the Catsper channel.

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“…Specific organs (lacrimal glands, mammary glands) from mice lacking Orai1, shown to completely lack store-operated entry develop normally but lack specific signaling functions [74,75]. However, other cell types show clear developmental deficiencies (skeletal muscle [72,76], sperm [77]).…”

Section: Cellular Function Of Store-operated Ca2+ Entrymentioning

confidence: 99%

The functions of store-operated calcium channels

Putney

Steinckwich-Besançon

Numaga‐Tomita

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Store-operated calcium channels provide calcium signals to the cytoplasm of a wide variety of cell types. The basic components of this signaling mechanism include a mechanism for discharging Ca2+ stores (commonly but not exclusively phospholipase C and inositol 1,4,5-trisphosphate), a sensor in the endoplasmic reticulum that also serves as an activator of the plasma membrane channel (STIM1 and STIM2), and the store-operated channel (Orai1, 2 or 3). The advent of mice genetically altered to reduce store-operated calcium entry globally or in specific cell types has provided important tools to understand the functions of these widely encountered channels in specific and clinically important physiological systems. This review briefly discusses the history and cellular properties of store-operated calcium channels, and summarizes selected studies of their physiological functions in specific physiological or pathological contexts.

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Male infertility in mice lacking the store-operated Ca2+ channel Orai1

Cited by 22 publications

References 35 publications

Effect of Protriptyline on [Ca^(2+)]i and Viability in MDCK Renal Tubular Cells

Effect of Protriptyline on [Ca^(2+)]i and Viability in MDCK Renal Tubular Cells

The Catsper channel and its roles in male fertility: a systematic review

The functions of store-operated calcium channels

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