Copper and protons directly activate the zinc-activated channel

Area of Science:

• Molecular biology
• Neuroscience
• Ion channel physiology

Background:

• The zinc-activated channel (ZAC) is a poorly understood member of the Cys-loop receptor superfamily.
• Cys-loop receptors are pentameric ligand-gated ion channels crucial for neuronal signaling.

Purpose of the Study:

• To further characterize the properties and gating mechanisms of the zinc-activated channel (ZAC).
• To identify novel agonists and understand the ion permeability and selectivity of ZAC.

Main Methods:

• Electrophysiological recordings to measure ion channel activity.
• Application of various cations (Zn2+, Cu2+, H+, Na+, K+, Cs+, Ca2+, Mg2+) to assess gating and permeability.
• Analysis of activation, decay kinetics, and agonist potency/efficacy.

Main Results:

• Zinc (Zn2+), copper (Cu2+), and protons (H+) were identified as agonists of ZAC, with potencies in the order H+ > Cu2+ > Zn2+.
• Agonist-gated currents exhibited low desensitization, but activation and decay kinetics differed significantly, especially for H+.
• ZAC demonstrated non-selective permeability to monovalent cations (Na+, K+, Cs+) but was inhibited by divalent cations (Ca2+, Mg2+).

Conclusions:

• This study reports for the first time that ZAC, a Cys-loop receptor, can be gated by Zn2+, Cu2+, and H+.
• ZAC's unique gating properties and ion selectivity suggest its potential role in physiological processes involving these ions.