A hyperpolarization- and acid-activated nonselective cation current in Xenopus oocytes

Area of Science:

• Membrane biophysics
• Ion channel physiology
• Xenopus oocyte expression systems

Background:

• A hyperpolarization-activated inward current (I(IN)) is observed in Xenopus oocytes expressing various membrane proteins.
• The ionic basis and characteristics of I(IN) are not fully understood, with conflicting reports suggesting it's a Cl current or a nonselective cation current.

Purpose of the Study:

• To comprehensively characterize the endogenous hyperpolarization-activated inward current (I(IN)) in Xenopus oocytes.
• To elucidate the ionic components and regulatory mechanisms of I(IN).

Main Methods:

• Electrophysiological recordings in Xenopus oocytes.
• Ionic substitution experiments to identify charge carriers.
• Chelation of intracellular calcium using BAPTA-AM.
• Intracellular acidification.
• Heterologous expression of transient receptor potential-like (TRPL) channels.

Main Results:

• I(IN) comprises a calcium (Ca) and magnesium (Mg) permeable cation current and a calcium-activated chloride (Cl) current under physiological conditions.
• The Ca-activated Cl current component was abolished by chelating cytosolic Ca.
• The cation current was permeable to Ca, Mg, and cobalt (Co), but not barium (Ba), manganese (Mn), or cadmium (Cd).
• I(IN) was potentiated by intracellular acidification.
• Heterologous expression of TRPL altered the voltage sensitivity of the endogenous I(IN).

Conclusions:

• The endogenous I(IN) in Xenopus oocytes is a complex current involving both cation and Ca-activated Cl flux.
• I(IN) exhibits distinct properties differing from store-operated Ca currents.
• TRPL expression can modulate the endogenous I(IN), suggesting interactions within the Xenopus oocyte system.