Supplementary Table 1. Classification of ion channels*
Class / Family:channel structure / Ion selectivity / Subfamily / IUPHAR
pore-forming subunits nomenclature / HUGO gene
nomenclature / Predominant expression / Primary physiological significance
Ligand-gated / Cys-loop:
homo- or hetero-pentamer of homologous subunits / Non-selective cationic / nAChR / α1..α9 / CHRNA1..
CHRNA9 / Skeletal muscle, nervous system / Fast synaptic transmission
β1..β4 / CHRNB1..
CHRNB4
Γ / CHRNG
Δ / CHRND
Ε / CHRNE
5-HT3R / 5-HT3A..
5-HT3E / HTR3A..
HTR3E / Nervous system
Cl--selective / GlyR / α1..α4 / GLRA1..
GLRA4
Β / GLRB
GABAAR / α1..α6 / GABRA1..
GABRR6
β1..β3 / GABRB1..
GABRB3
γ1.. γ3 / GABRG1..
GABRG3
Δ / GABRD
Ε / GABRE
Θ / GABRQ
Π / GABRP
GABACR / ρ1..ρ3 / GABRR1..
GABRR3
Glutamate: homo- or hetero-tetramer of homologous subunits / Non selective cationic with variable Ca2+ permea-bility / AMPA / GluR1..
GluR4 / GRIA1..
GRIA4
Kainate / GluR5..
GluR7 / GRIK1..
GRIK3
KA1, KA2 / GRIK4,
GRIK5
NMDA / NR1 / GRIN1
NR2A..
NR2D / GRIN2A..
GRIN2D
NR3A,
NR3B / GRIN3A,
GRIN3B
δ1, δ2 / GRID1, GRID2
Purinergic: homo- or hetero-trimer of homologous subunits / P2X / P2X1..
P2X7 / P2RX1..
P2RX7 / Ubiquitous / Peripheral synaptic transmission, sensory transduction, nociception, tissue regulation
Voltage-gated / Sodium (Nav):
homomer with or without auxiliary subunits / Na+-selective / TTX-
sensitive / Nav1.1..
Nav1.4 / SCN1A..
SCN4A / Nervous system, SkM (Nav1.4) / Excitability
Nav1.6 / SCN8A
Nav1.7 / SCN9A
TTX-
resistant / Nav1.5 / SCN5A / Cardiac
Nav1.8 / SCN10A / Sensory neurons
Nav1.9 / SCN11A
Calcium (Cav):
homomer with or without auxiliary subunits / Ca2+-selective / L-type / Cav1.1 / CACNA1S, / SkM / Excitability, Ca2+ signaling
Cav1.2 / CACNA1C / Cardiac, SmM, endocrine cells
Cav1.3 / CACNA1D / Nervous system
Cav1.4 / CACNA1F / Retina
P/Q-type / Cav2.1 / CACNA1A / Nervous system
N-type / Cav2.2 / CACNA1B
R-type / Cav2.3 / CACNA1E
T-type / Cav3.1 / CACNA1G / Ubiquitous
Cav3.2 / CACNA1H
Cav3.3 / CACNA1I
K+-permeable / Voltage-gated (Kv):
homo- or hetero-tetramer of homologous subunits with or without auxiliary subunits / K+-selective / Shaker-, Shab-, Shal-, Shaw-related and
their homologs / Kv1.1..
Kv1.7 / KCNA1..
KCNA7 / Ubiquitous, some have more specific tissue distribution / Excitability, K+ efflux
Kv1.8 / KCNA10
Kv2.1, Kv2.2 / KCNB1, KCNB2
Kv3.1..
Kv3.4 / KCNC1..
KCNC4
Kv4.1..
Kv4.3 / KCND1..
KCND3
Kv5.1 / KCNF1
Kv6.1..
Kv6.4 / KCNG1..
KCNG4
Kv8.1, Kv8.2 / KCNV1, KCNV2
Kv9.1..
Kv9.3 / KCNS1..
KCNS3
KvLQT1-related / Kv7.1..
Kv7.5 / KCNQ1..
KCNQ5
eag-related / Kv10.1 / KCNH1 / Brain, cancer tissues / Cell cycle & proliferation, ?
Kv10.2 / KCNH5 / Brain / ?
erg-related / Kv11.1 / KCNH2 / Heart & some cancers (Kv11.1), brain, some peripheral tissues / Cardiac repolarization (Kv11.1), ?
Kv11.2 / KCNH6
Kv11.3 / KCNH7
elc-related / Kv12.1 / KCNH8 / Brain, neuroblastoma, blood cells, leukemias / ?
Kv12.2 / KCNH3
Kv12.3 / KCNH4
Ca2+-activated (KCa):
homo- or hetero-tetramer of homologous subunits with or without auxiliary subunits / BKCa / KCa1.1 / KCNMA1 / Ubiquitous / Control of excitability, Vm feedback Ca2+ signaling
SKCa / KCa2.1..
KCa2.3 / KCNN1..
KCNN3
IKCa / KCa3.1 / KCNN4
Na+-, Cl--, votage-activated / KCa4.1, KCa4.2 / KCNT1, KCNT2 / Brain, kidney, testis, ubiquitous (KCa4.2) / ?
(OH)+-, votage-activated / KCa5.1 / KCNU1 / Testis, spermatosytes / ?
Inwardly rectifying (Kir):
homo- or hetero-tetramer of homologous subunits / Kir / Kir1.1 / KCNJ1 / Kidney / Vm regulation, excitability, K+ recycling, [K+]o clearance
Kir2.1 / KCNJ2 / Brain, heart, SkM, kidney
Kir2.2 / KCNJ12
Kir2.3 / KCNJ4
Kir2.4 / KCNJ14
Kir4.1 / KCNJ10 / Glia, retina
Kir4.2 / KCNJ15 / Kidney, pancreas, liver
Kir5.1 / KCNJ16 / Kidney, pancreas, retina liver, brain
Kir7.1 / KCNJ13
GIRK
(G protein-gated) / Kir3.1 / KCNJ3 / Brain / Receptor-dependent regulation of Vm and excitability
Kir3.2 / KCNJ6 / Ubiquitous
Kir3.3 / KCNJ9 / Brain
Kir3.4 / KCNJ5 / Heart, brain, SkM
KATP (ATP-dependent; in association with SUR subunits) / Kir6.1 / KCNJ8 / Vascular / Vm coupling to metabolic state, vascular tone, insulin secretion
Kir6.2 / KCNJ11 / Pancreas, heart, SkM, brain
Background (K2P):
homodimer, heterodime-rization of some subunits is assumed / K2P (two-pore-domain) / K2P1.1 / KCNK1 / Ubiquitous / K+ leak, Vm regulation in response to lipid messengers, physical and chemical characteristics of the medium
K2P2.1 / KCNK2 / Brain, heart
K2P3.1.. K2P7.1 / KCNK3.. KCNK7 / Ubiquitous
K2P9.1 / KCNK9 / Brain, cancer tissues
K2P10.1 / KCNK10 / Ubiquitous
K2P12.1 / KCNK12
K2P13.1 / KCNK13
K2P15.1..
K2P18.1 / KCNK15..
KCNK18 / Ubiquitous (K2P15.1), ouside CNS (K2P16.1, K2P17.1), CNS (K2P18.1)
Cyclic nucleotide-regulated / CNG:
homo- or hetero-tetramer / Non selective cationic / CNGA / CNGA1..
CNGA4 / CNGA1..
CNGA4 / Visual and olfactory systems, some neurons / Visual & olfactory transduction
CNGB / CNGB1 / CNGB1
CNGB3 / CNGB3
HCN:
homo- or hetero-tetramer / HCN / HCN1..
HCN4 / HCN1..
HCN4 / CNS, PNS, heart / Waves of Vm, periodic electrical activity
Store-operated / SOC: homo- or heteromer activated by STIM proteins / Ca2+-selective / Highly Ca2+-selective / Orai1..Orai3 / ORAI1.. ORAI3 / Ubiquitous / Store-operated Ca2+ entry
Transient receptor potential / TRP:
homo- or hetero-tetramer of homologous subunits / Non selective cationic with variable Ca2+ permea-bility / TRPC
(canonical) / TRPC1 / TRPC1 / Ubiquitous / Receptor-activated Ca2+ signaling, SOC constituents (?)
TRPC2 / TRPC2
TRPC3 / TRPC3
TRPC4 / TRPC4
TRPC5 / TRPC5
TRPC6 / TRPC6
TRPC7 / TRPC7
TRPV
(vanilloid) / TRPV1 / TRPV1 / Sensory neurons, CNS / Detection of heat/warmth, nociception, Ca2+ signaling
TRPV2 / TRPV2
TRPV3 / TRPV3
TRPV4 / TRPV4 / Ubiquitous / Osmosensor
TRPV5 / TRPV5 / GI tract, kidney, pancreas, prostate / Epithelial Ca2+ transporters, Ca2+ signaling
TRPV6 / TRPV6
TRPM
(melastatin) / TRPM1 / TRPM1 / Brain, melanosomes / Translocation
TRPM2 / TRPM2 / Brain, spleen / Redox sensor
TRPM3 / TRPM3 / Brain, kidney / Osmosensor
TRPM4 / TRPM4 / Colon, prostate / Ca2+-, voltage-, PIP2-modulated
TRPM5 / TRPM5 / Intestine, liver
TRPM6 / TRPM6 / Kidney, intestine, heart / Mg2+-inhibited
TRPM7 / TRPM7
TRPM8 / TRPM8 / Sensory neurons, prostate / Cold sensor
TRPA
(ankyrin) / TRPA1 / TRPA1 / Sensory neurons / Irritants sensor, inflammatory pain
TRPP
(polycystin) / TRPP1 / PKD2 / Ubiquitous, kidney / Ca2+-, fluid flow-, PIP2-modulated
TRPP2 / PKD2L1 / Kidney, heart, testis
TRPP3 / PKD2L2
TRPML
(mucolipin) / TRPML1..
TRPML3 / MCOLN1..
MCOLN3 / Brain, heart, SkM, cochlear (TRPML3) / pH-, Ca2+-sensing, (?)
Sodium non-voltage-gated, degenerin(DEG)-related / Epithelial: homo- or hetero-tetramer / Na+-selective / ENaC / ENaCα / SCNN1A / Glandular & visceral epithelium / Transepithelial Na+ transport
ENaCβ / SCNN1B
ENaCγ / SCNN1G
ENaCδ / SCNN1D
Proton-gated: homo- or hetero-tetramer / ASIC / ASIC1 / ACCN1 / PNS, CNS, retina, taste cells, cochlear / Nociception, synaptic plasticity, mechanoper-ception, hearing, visual transduction
ASIC2 / ACCN2
ASIC3 / ACCN3
ASIC4 / ACCN4
Anion / ClC: homo- or hetero-dimer with or without auxiliary subunits / Cl--selective / PM Cl- channels / ClC-1 / CLCN1 / SkM / Vm stabilization
ClC-2 / ClCN2 / Ubiquitous / Transepithelial Cl- transport, volume regulation
ClC-Ka, ClC-Kb / CLCNKA, CLCNKB / Kidney, inner ear / Renal salt reuptake
Endo-, lysosomal Cl-/H+ exchangers and Cl- channels / ClC-3 / CLCN3 / Ubiquitous / Endo-, lysosomal acidification, volume regulation (ClC-3 ?)
ClC-4..
ClC-7 / CLCN4..
ClCN7
ABC: homomer / ABCC / CFTR / ABCC7 / Lung, secretory epithelia / Transepithelial Cl- transport
VRAC: not known / ? / ClC-2 (?), ClC-3 (?), PLM (?), ICln (?) / CLCN2, CLCN3, FXYD1, CLNS1A / Ubiquitous / RVD (?)
CaCC: not known / ? / CLCA1 (?),
BEST1 (?) / CLCA1, BEST1 / Ubiquitous / Vm regulation, epithelial salt transport
*The table lists major classes, families, subfamilies and individual pore-forming subunits of known plasma membrane ion channels together with their preferential ion selectivity, predominant tissue distribution and primary physiological significance. Functional ion channel is commonly composed of several identical (homomultimer) or homologous (heteromultimer) pore-forming subunits with or without auxiliary, non-pore-forming subunits (not listed in this Table). Some pore-forming subunints are unable to form functional channel, but can do so in combination with other homologous subunits (i.e., can only be a part of heteromultimer). Only unifying IUPHAR (International Union of Basic and Clinical Pharmacology) channel subunits nomenclature together with HUGO (Human Genome Organization) nomenclature of respective genes are presented. For alternative designations of the channels specifically involved in cancer hallmarks see Table 2. Only first and last members of homologous subunits/genes separated by two periods are shown if their designation includes sequential numbering or lettering. Question mark depicts controversial results or lack thereof. Abbreviations: ABC – ATP-binding cassette, AMPA – α-amino-3-hydroxy-5-methyl-1-4-isoxazole propionate, ASIC – acid-sensing ion channel, CaCC – Ca2+-activated Cl- channel, CFTR – cystic fibrosis transmembrane regulator, ClC – Cl- channel, CNG – cyclic nucleotyde-gated, CNS – central nervous system, ENaC – epithelial Na+ channel, GABAA/CR – gamma-aminobutyric acid receptor type A or C, GI – gastro intestinal, GlyR – glycine receptor, HCN – hyperpolarization-activated cyclic nucleotyde-modulated, 5-HT3R – 5-hydroxytryptamine (serotonin) receptor type 3, nAChR – nicotinic acetycholine (ACh) receptor, NMDA – N-Methyl-D-aspartate, PIP2 – phosphoinositide-4,5-bisphosphate, PM – plasma membrane, PNS – peripheral nervous system, P2X – purinergic type 2X, SkM – skeletal muscle, SmM – smooth muscle, RVD – regulatory volume decrease, SUR – sulfonylurea receptor, TRP – transient receptor potential, TTX – tetrodotoxin, Vm – membrane potential, VRAC – volume-regulated anion channel, ion symbol in square brackets with subscript “i” or “o” denotes its intracellular or extracellular concentration, respectively.
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