scholarly journals Signalling pathways involved in the control of sperm cell volume

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 61-73 ◽  
Author(s):  
A M Petrunkina ◽  
R A P Harrison ◽  
M Tsolova ◽  
E Jebe ◽  
E Töpfer-Petersen
Keyword(s):  
Ion Channels ◽  
Cell Volume ◽  
Protein Phosphatase ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Regulatory Volume Decrease ◽  
Phosphatase Inhibitors ◽  
Protein Phosphatase Inhibitors ◽  
Negative Effect ◽  
Volume Measurements

The ability to maintain cellular volume is an important general physiological function, which is achieved by specific molecular mechanisms. Hypotonically induced swelling results in the opening of K+and Cl−ion channels, through which these ions exit with accompanying water loss. This process is known as regulatory volume decrease (RVD). The molecular mechanisms that control the opening of the ion channels in spermatozoa are as yet poorly understood. The present study investigated pathways of osmo-signalling using boar spermatozoa as a model. Spermatozoa were diluted into isotonic and hypotonic Hepes-buffered saline in the presence or absence of effector drugs, and at predetermined intervals volume measurements were performed electronically. Treatment with protein kinase C (PKC) inhibitors staurosporine, bismaleimide I and bismaleimide X led to dose-dependent increases of both isotonic and hypotonic volumes (P<0.05). However, as the isotonic volume was affected more than the hypotonic volume, the kinase inhibitors appeared to improve RVD, whereas activation of PKC with phorbol dibutyrate blocked RVD. The increase in isotonic cell volume induced by bismaleimide X was observed in chloride-containing medium but not in the medium in which chloride was replaced by sulphate, implying that PKC was involved in the control of chloride channel activity, e.g. by closing the channel after volume adjustment. The protein phosphatase PP1/PP2 inhibitors calyculin and okadaic acid increased the isotonic volume only slightly but they greatly increased the relative cell volume and blocked RVD. The activation of RVD processes was found to be cAMP-dependent; incubation with forskolin and papaverine improved volume regulation. Moreover, papaverine was able to overcome the negative effect of protein phosphatase inhibitors. The mechanism of sperm RVD appears to involve (a) alterations in protein phosphorylation/dephosphorylation balance brought about by PKC and PP1 and (b) a cAMP-dependent activating pathway.

Effects of Serine/Threonine Protein Phosphatases on Ion Channels in Excitable Membranes

2000 ◽  
Vol 80 (1) ◽  
pp. 173-210 ◽  
Author(s):  
Stefan Herzig ◽  
Joachim Neumann
Keyword(s):  
Ion Channels ◽  
Protein Phosphatase ◽  
Protein Phosphatases ◽  
Direct Interaction ◽  
Specific Protein ◽  
Biochemical Properties ◽  
Future Research ◽  
Regulatory Subunits ◽  
Phosphatase Inhibitors ◽  
Protein Phosphatase Inhibitors

This review deals with the influence of serine/threonine-specific protein phosphatases on the function of ion channels in the plasma membrane of excitable tissues. Particular focus is given to developments of the past decade. Most of the electrophysiological experiments have been performed with protein phosphatase inhibitors. Therefore, a synopsis is required incorporating issues from biochemistry, pharmacology, and electrophysiology. First, we summarize the structural and biochemical properties of protein phosphatase (types 1, 2A, 2B, 2C, and 3–7) catalytic subunits and their regulatory subunits. Then the available pharmacological tools (protein inhibitors, nonprotein inhibitors, and activators) are introduced. The use of these inhibitors is discussed based on their biochemical selectivity and a number of methodological caveats. The next section reviews the effects of these tools on various classes of ion channels (i.e., voltage-gated Ca2+ and Na+ channels, various K+ channels, ligand-gated channels, and anion channels). We delineate in which cases a direct interaction between a protein phosphatase and a given channel has been proven and where a more complex regulation is likely involved. Finally, we present ideas for future research and possible pathophysiological implications.

scholarly journals Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume Regulation

2021 ◽  
Vol 9 ◽  
Author(s):  
Yizeng Li ◽  
Xiaohan Zhou ◽  
Sean X. Sun
Keyword(s):  
Ion Channels ◽  
Cell Volume ◽  
Volume Regulation ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Water Flux ◽  
Cell Volume Regulation ◽  
Sodium Potassium ◽  
Before And After

Cells lacking a stiff cell wall, e.g., mammalian cells, must actively regulate their volume to maintain proper cell function. On the time scale that protein production is negligible, water flow in and out of the cell determines the cell volume variation. Water flux follows hydraulic and osmotic gradients; the latter is generated by various ion channels, transporters, and pumps in the cell membrane. Compared to the widely studied roles of sodium, potassium, and chloride in cell volume regulation, the effects of proton and bicarbonate are less understood. In this work, we use mathematical models to analyze how proton and bicarbonate, combined with sodium, potassium, chloride, and buffer species, regulate cell volume upon inhibition of ion channels, transporters, and pumps. The model includes several common, widely expressed ion transporters and focuses on obtaining generic outcomes. Results show that the intracellular osmolarity remains almost constant before and after cell volume change. The steady-state cell volume does not depend on water permeability. In addition, to ensure the stability of cell volume and ion concentrations, cells need to develop redundant mechanisms to maintain homeostasis, i.e., multiple ion channels or transporters are involved in the flux of the same ion species. These results provide insights for molecular mechanisms of cell volume regulation with additional implications for water-driven cell migration.

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