Induction of a Sodium-dependent Depolarization by External Calcium Removal in Human Sperm

González-Martı́nez, Marco T.

doi:10.1074/jbc.m304479200

Cited by 22 publications

(38 citation statements)

References 31 publications

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“…This characteristic of CatSper, which is a result of divalent cation binding within the channel pore, can explain earlier observations which showed that divalent cation-free (or depleted) medium causes enhanced Na + influx and depolarization of human sperm (Gonzáles-Martinez, 2003; Torres-Flores et al , 2011) and can also account for the loss of K + versus Na + selectivity that we observed in medium devoid of divalent cations medium. However, NNC55-0396 and mibefradil, structurally related compounds that block CatSper, suppressed the hyperpolarizing K + recorded under standard (physiological) conditions.…”

Section: Discussionsupporting

confidence: 83%

Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels

Mansell

Publicover

Barratt³

et al. 2014

Molecular Human Reproduction

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Whilst fertilizing capacity depends upon a K+ conductance (GK) that allows the spermatozoon membrane potential (Vm) to be held at a negative value, the characteristics of this conductance in human sperm are virtually unknown. We therefore studied the biophysical/pharmacological properties of the K+ conductance in spermatozoa from normal donors held under voltage/current clamp in the whole cell recording configuration. Our standard recording conditions were designed to maintain quasi-physiological, Na+, K+ and Cl− gradients. Experiments that explored the effects of ionic substitution/ion channel blockers upon membrane current/potential showed that resting Vm was dependent upon a hyperpolarizing K+ current that flowed via channels that displayed only weak voltage dependence and limited (∼7-fold) K+ versus Na+ selectivity. This conductance was blocked by quinidine (0.3 mM), bupivacaine (3 mM) and clofilium (50 µM), NNC55-0396 (2 µM) and mibefradil (30 µM), but not by 4-aminopyridine (2 mM, 4-AP). Progesterone had no effect upon the hyperpolarizing K+ current. Repolarization after a test depolarization consistently evoked a transient inward ‘tail current’ (ITail) that flowed via a second population of ion channels with poor (∼3-fold) K+ versus Na+ selectivity. The activity of these channels was increased by quinidine, 4-AP and progesterone. Vm in human sperm is therefore dependent upon a hyperpolarizing K+ current that flows via channels that most closely resemble those encoded by Slo3. Although 0.5 µM progesterone had no effect upon these channels, this hormone did activate the pharmacologically distinct channels that mediate ITail. In conclusion, this study reveals three functionally and pharmacologically distinct cation channels: Ik, ITail, ICatSper.

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Section: Discussionsupporting

confidence: 83%

Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels

Mansell

Publicover

Barratt³

et al. 2014

Molecular Human Reproduction

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“…Li ϩ can replace Na ϩ ; thus, these findings suggest that a Na ϩ -and Li ϩ -permeable electrogenic pathway may be present in mammalian sperm (19). The present work explores this later possibility.…”

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confidence: 76%

Sodium and Epithelial Sodium Channels Participate in the Regulation of the Capacitation-associated Hyperpolarization in Mouse Sperm

Hernández‐González

Sosnik

Edwards

et al. 2006

Journal of Biological Chemistry

117

149

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In a process called capacitation, mammalian sperm gain the ability to fertilize after residing in the female tract. During capacitation the mouse sperm plasma membrane potential (E m ) hyperpolarizes. However, the mechanisms that regulate sperm E m are not well understood. Here we show that sperm hyperpolarize when external Mammalian sperm are not able to fertilize after ejaculation. They acquire this ability only after residing in the female uterine tract for a finite period of time that varies depending on the species. The molecular, biochemical, and physiological changes that occur in sperm while in the female tract are collectively referred to as capacitation (1). Capacitation is associated with changes in membrane properties, enzyme activities, and motility that prepare the sperm for the acrosome reaction and for penetration of the egg vestments prior to fertilization. The molecular basis of capacitation has been partially defined and includes: the removal of cholesterol from the sperm plasma membrane by cholesterol acceptors such as bovine serum albumin (2, 3), modifications in plasma membrane phospholipids, fluxes of HCO 3 Ϫ (4) and other intracellular ions, and increased tyrosine phosphorylation of proteins (5-7). These events are likely to play a role in the induction of hyperactivated motility and the ability of the sperm to undergo a regulated acrosome reaction (for review see Ref. 8).Bovine and mouse sperm capacitation is also accompanied by a plasma membrane hyperpolarization. E m decreases in mouse sperm from Ϫ38 to Ϫ55 mV (4, 9, 10) and in bovine sperm from Ϫ33 to Ϫ66 mV (9). Because capacitation prepares sperm for the acrosome reaction, the capacitation-associated hyperpolarization may regulate the ability of sperm to generate transient Ca 2ϩ elevations during the acrosome reaction induced by physiological agonists (e.g. zona pellucida) (11). In this respect, low voltage-activated T-type Ca 2ϩ channels have been detected in mouse spermatogenic cells (12, 13), and these channels are also present in mature mouse sperm (14, 15). One unique property of low voltage-activated Ca 2ϩ channels is that they inactivate at the resting E m of sperm prior to capacitation (around Ϫ35 mV) (12,14). Thus, if low voltage-activated Ca 2ϩ channels are involved in the regulation of the acrosome reaction, the capacitation-associated sperm hyperpolarization may be required to remove this inactivation (11,16,17).Although the molecular mechanisms by which the sperm E m hyperpolarizes during capacitation are not clear, there exist several potential candidates. demonstrated with patch clamp techniques that inward rectifying K ϩ channels are expressed in mouse spermatogenic cells and proposed that these channels may contribute to the capacitation-associated sperm membrane hyperpolarization. An increase in sperm K ϩ permeability should lead to an E m hyperpolarization, according to the K ϩ equilibrium potential (18). Alternatively, the sperm plasma membrane may become less permeable to Na ϩ . The relatively depolarized mamma...

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“…In light of the results presented here, if calcium influx through VDCC contributes to resting [Ca 2ϩ ] i , the small but biologically significant increase in [Ca 2ϩ ] i observed during capacitation could be related to the VDCC stimulation reported here. Other putative non-voltagedependent calcium channels have been considered as mechanisms to set the resting [Ca 2ϩ ] i (11).…”

Section: Discussionmentioning

confidence: 99%

“…There is a linear relationship between the fractional change of diSC 3(5) fluorescence, f Ϫ fo/fo (where fo is fluorescence in the presence of valinomycin addition and f are actual fluorescence values), and E k (23). Consequently, f can be converted to V m according to the following equation (11): Vm ϭ f/mf o Ϫ 1/m Ϫ b/m, where m and b are parameters of the linear calibration curve, that is, the slope and the fractional change of fluorescence at 0 mV, respectively.…”

Section: Methodsmentioning

confidence: 99%

Effect of intracellular pH on depolarization-evoked calcium influx in human sperm

Fraire-Zamora¹,

González-Martı́nez²

2004

American Journal of Physiology-Cell Physiology

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Human sperm are endowed with putative voltage-dependent calcium channels (VDCC) that produce measurable increases in intracellular calcium concentration ([Ca(2+)](i)) in response to membrane depolarization with potassium. These channels are blocked by nickel, inactivate in 1-2 min in calcium-deprived medium, and are remarkably stimulated by NH(4)Cl, suggesting a role for intracellular pH (pH(i)). In a previous work, we showed that calcium permeability through these channels increases approximately onefold during in vitro "capacitation," a calcium-dependent process that sperm require to fertilize eggs. In this work, we have determined the pH(i) dependence of sperm VDCC. Simultaneous depolarization and pH(i) alkalinization with NH(4)Cl induced an [Ca(2+)](i) increase that depended on the amount of NH(4)Cl added. VDCC stimulation as a function of pH(i) showed a sigmoid curve in the 6.6-7.2 pH(i) range, with a half-maximum stimulation at pH approximately 7.00. At higher pH(i) (> or =7.3), a further stimulation occurred. Calcium release from internal stores did not contribute to the stimulating effect of pH(i) because the [Ca(2+)](i) increase induced by progesterone, which opens a calcium permeability pathway that does not involve gating of VDCC, was unaffected by ammonium. The ratio of pH(i)-stimulated-to-nonstimulated calcium influx was nearly constant at different test depolarization values. Likewise, depolarization-induced calcium influx in pH(i)-stimulated and nonstimulated cells was equally blocked by nickel. In our capacitating conditions pH(i) increased 0.11 pH units, suggesting that the calcium influx stimulation observed during sperm capacitation might be partially caused by pH(i) alkalinization. Additionally, a calcium permeability pathway triggered exclusively by pH(i) alkalinization was detected.

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Induction of a Sodium-dependent Depolarization by External Calcium Removal in Human Sperm

Cited by 22 publications

References 31 publications

Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels

Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels

Sodium and Epithelial Sodium Channels Participate in the Regulation of the Capacitation-associated Hyperpolarization in Mouse Sperm

Effect of intracellular pH on depolarization-evoked calcium influx in human sperm

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