Hepatic taurocholate uptake is electrogenic and influenced by transmembrane potential difference

Area of Science:

• Hepatobiliary Physiology
• Membrane Transport
• Electrophysiology

Background:

• Hepatocyte uptake of bile acids like taurocholate is crucial for bile acid homeostasis.
• This uptake is known to be coupled with sodium (Na+) influx.
• The precise stoichiometry and the role of the transmembrane electrical potential difference (PD) remain incompletely understood.

Purpose of the Study:

• To investigate the relationship between taurocholate extraction and the electrical potential difference (PD) across the hepatocyte membrane.
• To elucidate the influence of PD on the Na+-coupled uptake of taurocholate.
• To quantify taurocholate-induced transport currents in hepatocytes.

Main Methods:

• Utilized perfused liver models to measure taurocholate extraction and PD using intracellular microelectrodes.
• Employed patch-clamp recording techniques on cultured hepatocytes to measure taurocholate-induced transport currents.
• Manipulated Na+ gradients and ion concentrations (Cl-, nitrate) to alter PD and assess effects on taurocholate uptake.

Main Results:

• Decreased Na+ gradients and membrane depolarization significantly reduced taurocholate extraction in perfused livers.
• Depolarization induced by Cl- or nitrate substitution also decreased taurocholate extraction.
• Taurocholate exposure caused concentration-dependent membrane depolarization in a Na+-dependent manner.
• Patch-clamp studies revealed Na+-dependent inward currents in response to taurocholate, which varied with holding potential.

Conclusions:

• The transmembrane electrical potential difference (PD) plays a significant role in regulating Na+-coupled taurocholate uptake by hepatocytes.
• Taurocholate transport is electrogenic and directly influenced by membrane potential.
• These findings clarify the mechanism of bile acid transport and its dependence on cellular electrophysiology.