Modulation of the hepatocyte rough endoplasmic reticulum single chloride channel by nucleotide–Mg2+ interaction

Abstract

The effect of nucleotides on single chloride channels derived from rat hepatocyte rough endoplasmic reticulum vesicles incorporated into bilayer lipid membrane was investigated. The single chloride channel currents were measured in 200/50 mmol/l KCl cis/trans solutions. Adding 2.5 mM adenosine triphosphate (ATP) and adenosine diphosphate (ADP) did not influence channel activity. However, MgATP addition inhibited the chloride channels by decreasing the channel open probability (Po) and current amplitude, whereas mixture of Mg(2+) and ADP activated the chloride channel by increasing the Po and unitary current amplitude. According to the results, there is a novel regulation mechanism for rough endoplasmic reticulum (RER) Cl(-) channel activity by intracellular MgATP and mixture of Mg(2+) and ADP that would result in significant inhibition by MgATP and activation by mixture of Mg(2+) and ADP. These modulatory effects of nucleotide-Mg(2+) complexes on chloride channels may be dependent on their chemical structure configuration. It seems that Mg-nucleotide-ion channel interactions are involved to produce a regulatory response for RER chloride channels.

New and notable ion‐channels in the sarcoplasmic/endoplasmic reticulum: do they support the process of intracellular Ca2+ release?

“…But if this was their only role, then why does the SR contain so many different types of anion channel? An interesting report of a Cl − channel from liver rough ER that was activated by Mg 2+ -ADP and inhibited by Mg 2+ -ATP, suggested that this Cl − channel could be activated by metabolic stress (Ashrafpour et al 2012). The need for further study in this area is obvious and it must begin with identification of the proteins that constitute the SR Cl − channels so that structure-function studies can begin.…”