36 - Regulation of Ion Channels by Membrane Proteins and Cytoskeleton

Abstract

This chapter discusses the regulation of ion channels by membrane proteins and cytoskeleton. The chapter provides a synopsis of the effects of cytoskeleton on ion channels. The cytoskeleton regulates ion channel function through integrated interactions with cytoskeleton-associated proteins, as well as dynamic regulation of its own state. Two main roles of the cytoskeleton in the regulation of ion channel function are targeted distribution of ion channel proteins within specialized domains of plasma membranes, and modulation of ion channel activity. The structural interactions between the cytoskeleton, cytoskeleton associated proteins, and channel/receptor subunits determine the highly specialized distribution of ion channel proteins within certain domains of plasma membranes. It is known that domain-specific ion channel clustering of nicotinic aeetyleholine receptors (nAChRs) at the neuromuscular junction is essential for synaptic efficacy during neurotransmission. The chapter discusses several concepts, including rapsyn and clustering of nicotinic acetylcholine receptors at the neuromuscular junction, ankyrin and Na+ channels in the node of ranvier, and tyrosine kinase activity and clustering of nicotinic acetylcholine receptors. Based on the current understanding of the relationship between the cytoskeleton and ion channels, it is clear that modulation of the cytoskeleton and associated proteins may represent an important means of regulating the physiology of ion channels, and thereby cellular functions, including signaling and excitability. Disturbances of the cytoskeleton or associated proteins can occur under disease conditions, including muscular dystrophies, as well as under pathophysiological conditions, such as ischemia and hypoxia. It is understood that under such conditions the distribution and behavior of ion channels, which depend on the integrity of cytoskeleton networks, could be dramatically altered. The effects of cytoskeleton and ion channel function in disease states await to be analyzed.