Abstract
Calmodulin (CaM) is a small protein that acts as a ubiquitous signal transducer and regulates neuronal plasticity, muscle contraction, and immune response. It interacts with ion channels and plays regulatory roles in cellular electrophysiology. CaM modulates the voltage-gated sodium channel gating process, alters sodium current density, and regulates sodium channel protein trafficking and expression. Many mutations in the CaM-binding IQ domain give rise to diseases including epilepsy, autism, and arrhythmias by interfering with CaM interaction with the channel. In the present review, we discuss CaM interactions with the voltage-gated sodium channel and modulators involved in CaM regulation, as well as summarize CaM-binding IQ domain mutations associated with human diseases in the voltage-gated sodium channel family.
Highlights
The voltage-gated sodium channel (Nav ) plays a vital role in the generation and propagation of action potential in excitable cells such as neurons and cardiac myocytes [1].The family of voltage-gated sodium channels has nine members named Nav 1.1 throughNav 1.9 [2]
In addition to the IQ domain, a globular domain in the C-terminus of voltage-gated sodium channel consists of EF hand-like (EFL) motifs that interact with CaM in the absence of
Nav 1.8-R1869C and Nav 1.8-R1869G disrupted CaM-induced hyperpolarization shift and attenuated effects of CaM on development and recovery from slow inactivation [60]. These results suggested that Nav 1.8 IQ domain mutations weakened the interaction between CaM and Nav 1.8 channel and perturbed CaM regulation of Nav 1.8 function
Summary
The voltage-gated sodium channel (Nav ) plays a vital role in the generation and propagation of action potential in excitable cells such as neurons and cardiac myocytes [1]. CaM is a small protein expressed in all eukaryotic cells [12] It acts as a ubiquitous signal transducer and regulates essential processes such as neuronal plasticity, muscle contraction, and immune response [13]. Three isoforms (Nav1.7, Nav1.8, and Nav1.9) are widely expressed in neurons of the peripheral nervous system, such as dorsal root ganglia (DRG) neurons [5,6,7]. IQ domain is located within the C-terminal www.mdpi.com/journal/ijms domain of the voltagegated sodium channel It contains around 25 residues with two highly conserved amino acids, isoleucine (I) and glutamine (Q), in the middle of the motif. In addition to the IQ domain, a globular domain in the C-terminus of voltage-gated sodium channel consists of EF hand-like (EFL) motifs that interact with CaM in the absence of.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
