Biomedical Engineering Reference
In-Depth Information
SSS
Sick sinus syndrome
TCAs
Tricyclic antidepressants
TTX
Tetrodotoxin
VGSCs
Voltage-gated sodium channels
1
Introduction: A Brief Mention of All Ion Channels
Ion channels are membrane protein complexes allowing the passive flow of ions
across biological membranes [
1
]. Differently from ion pumps, ion channels
do not use the energy of ATP hydrolysis to transport ions against their electro-
chemical gradient. The majority of ion channels possess a pore loop, a region of
the protein that repeatedly crosses the membrane to form the selectivity filter
that discriminates among ion species. The passage of a specific ion takes place
when the channel is open. The conformational change between closed and open
state is called gating. Channel gating is controlled by multiple factors and ion
channels can be classified according to which chemical or physical modulator
controls their gating activity. The most common groups of channels are listed
as follows:
- Voltage-gated channels [voltage-gated potassium channels, voltage-gated
sodium channels, voltage-gated calcium channels], whose gating mechanism is
guided by membrane potential
- Ligand-gated channels [nicotinic acetylcholine receptors (nAChRs), ionotropic
glutamate receptors (NMDA, AMPA, Kainate), GABA
A
receptors, glycine
strychinine-sensitive receptors (GlyR), ATP-gated P2X receptors, and the
5-HT
3
serotonin receptor], whose gating mechanism is guided by a ligand
- Mechanosensitive channels, for which gating occurs in response to variation in
osmotic pressure and membrane curvature
By regulating ion fluxes, ion channels govern membrane potential and
excitability, determine the shape of the action potential, trigger muscle contraction
and exocytosis (through Ca
2+
influx), keep cell volume under control and are
involved in many other cellular processes. As a consequence to that, they play
important roles in multiple physiological processes as nerve and muscle excitation,
hormone secretion, cell proliferation, sensory transduction, learning and memory,
regulation of blood pressure, salt and water balance, lymphocyte proliferation,
fertilization, and cell death. Noteworthy, abnormalities in ion channel expression,
structure and function are tightly related to pathological states present in a number
of disorders. Therefore, we can conclude that due to their important functional
roles, their membrane location, structural heterogeneity and the specific tissue
expression of some channel types, ion channels represent interesting targets for
drug discovery. In this chapter, we focus our attention on voltage-gated sodium
channels (VGSCs).
