Alanine uptake activates hepatocellular chloride channels

Area of Science:

• Cellular physiology
• Membrane transport
• Ion channel function

Background:

• Cells increase in size upon amino acid uptake, necessitating adaptive volume regulatory mechanisms.
• Adaptive responses to cell swelling are hypothesized to involve increased ion permeability via volume-sensitive channels.
• Previous research primarily used hypotonic swelling models, which are less relevant to in vivo conditions.

Purpose of the Study:

• To investigate volume regulatory responses in hepatocytes during physiological amino acid uptake.
• To identify the ion channels involved in adaptive volume regulation following amino acid transport.
• To explore the role of volume-sensitive anion channels in response to nutrient intake.

Main Methods:

• Utilized immortalized hepatocytes as a model system for studying cell swelling.
• Examined cellular volume changes and membrane currents in response to alanine uptake.
• Characterized the properties of the observed chloride currents, including ion dependence, rectification, and blocker sensitivity.

Main Results:

• Alanine-induced cell swelling was followed by a decrease in cell volume.
• This volume decrease was associated with increased membrane chloride currents.
• The chloride currents were dependent on alanine concentration and sodium, suggesting stimulation by Na+-coupled alanine uptake.
• Currents exhibited outward rectification and an anion permeability sequence of I- > Br- > Cl-.
• The chloride channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid inhibited these currents.

Conclusions:

• Volume-sensitive anion channels are activated during physiological amino acid uptake in hepatocytes.
• These channels play a crucial role in the adaptive volume regulatory response to amino acid transport.
• The findings provide a new physiological context for the function of volume-sensitive anion channels beyond hypotonic stress.