Ion channels of mitochondrial membranes

Abstract

This chapter describes the third class of membrane transporters, comprised of channels or pores, entities that define water-filled transmembrane pathways of varying size and selectivity. Numerous channel activities have been detected by application of bilayer and patch-clamp methodologies to mitochondrial membranes. In the outer membrane, the main channel activity is that of the porin, voltage-dependent anion channels (VDAC), and a voltage-gated large conductance channel. It is likely that this channel represents the primary permeability pathway through the outer membrane for metabolites and ions. The modulation of the VDAC channel by endogenous effectors suggests a regulatory role for outer membrane permeability in mitochondrial metabolism. A second large-conductance outer-membrane channel activity has been detected and may be involved in protein import. Five inner-membrane channel activities have been described based on patch-clamp studies of mitoplasts. The first discovered was mCS, a voltage-dependent 100pS anion channel activity that co-isolates with the ATP synthase. The multi conductance channel (MCC) activity has a maximum conductance twice that of VDAC and appears to correspond to the calcium- and cyclosporin-sensitive permeability transition pore (PTP) deduced from swelling studies. There are several indications that MCC and VDAC interact at a drug-receptor complex located at intermembrane contact sites. Three low-conductance channel activities have been detected in the mitochondrial inner membrane: a glibenclamide- and adenosine triphosphate (ATP)-sensitive K + channel, and two pH-sensitive channel activities with opposite ion selectivity. The inner membrane ion channels appear to be highly regulated and are not expected to be open continuously under normal conditions.