Block of mouse Slo1 and Slo3 K+ channels by CTX, IbTX, TEA, 4-AP and quinidine.
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Differential differences in pharmacological properties of Slo3 and Slo1 currents are defined, blockade in terms of distinct blocking models are examined, and mutated constructs are used to evaluate determinants of block.Abstract:
pH-regulated Slo3 channels, perhaps exclusively expressed in mammalian sperm, may play a role in alkalization-mediated K(+) fluxes associated with sperm capacitation. The Slo3 channel shares extensive homology with Ca(2+)- and voltage-regulated BK-type Slo1 K(+) channels. Here, using heterologous expression in oocytes, we define distinctive differences in pharmacological properties of Slo3 and Slo1 currents, examine blockade in terms of distinct blocking models, and, for some blockers, use mutated constructs to evaluate determinants of block. Slo3 is resistant to block by the standard Slo1 blockers, iberiotoxin, charybdotoxin and extracellular TEA. Slo3 is relatively insensitive to extracellular 4-AP up to 100 mM, while Slo1 is blocked in a voltage-dependent fashion consistent with block on the extracellular side of the channel. Block of both Slo1 and Slo3 by cytosolic 4-AP can be described by open channel block, with Slo3 being approximately 10-15-fold more sensitive, but exhibiting weaker voltage-dependence of block. The cytosolic concentrations of 4-AP required to block Slo3 make it unlikely that the effects of 4-AP on volume regulation in mammalian sperm is mediated by Slo3. Quinidine was more effective in blocking Slo3 than Slo1. For Slo1, quinidine block was favored by depolarization, irrespective of the side of application. For Slo3, quinidine block was relieved by depolarization, irrespective of the side of application, with strong block by less than 10 microM quinidine at potentials near 0 mV. The unusual voltage-dependence of block of Slo3 by quinidine may result from preferential binding of quinidine to closed Slo3 channels. The quinidine concentrations effective in blocking Slo3 suggest, that in experiments that have examined quinidine effects on sperm, any Slo3 currents would be almost completely inhibited.read more
Citations
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The control of male fertility by spermatozoan ion channels.
TL;DR: How ion channels regulate sperm physiology is discussed, including mutations and deletions in sperm-specific ion channels affect male fertility in both mice and humans without affecting other physiological functions.
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K+ Channels: Function-Structural Overview
Carlos Gonzalez,David Baez-Nieto,Ignacio Valencia,Ingrid Oyarzún,Patricio Rojas,David Naranjo,Ramon Latorre +6 more
TL;DR: The present overview discusses in the function, localization, and the relations between function and structure of the five different subfamilies of K(+) channels: (a) inward rectifiers, Kir; (b) four transmembrane segments-2 pores, K2P; (c) voltage-gated, Kv; (d) the Slo family; and (e) Ca(2+)-activated SK family, SKCa.
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Deletion of the Slo3 gene abolishes alkalization-activated K+ current in mouse spermatozoa.
TL;DR: KSper/Slo3 is the primary spermatozoan K+ current, that KSper may play a critical role in acquisition of normal morphology and sperm motility when faced with hyperosmotic challenges, and that Slo3 is critical for fertility.
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Ca2+ Signals Generated by CatSper and Ca2+ Stores Regulate Different Behaviors in Human Sperm
Wardah Abdullah Alasmari,Sarah Costello,Joao Correia,Senga K. Oxenham,Jennifer Morris,Leonor Fernandes,João Ramalho-Santos,Jackson Kirkman-Brown,Francesco Michelangeli,Stephen J. Publicover,Christopher L.R. Barratt +10 more
TL;DR: It is proposed that CatSper activation can elicit functionally different behaviors according to the sensitivity of the Ca2+ store, which may be regulated by capacitation and NO from the cumulus.
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Flagellar ion channels of sperm: similarities and differences between species.
TL;DR: The current knowledge about ion channel diversity of the animal kingdom is summarized and attention is focused on flagellar ion channels of mammalian sperm.
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