Oláh, Szöllősi, Bíró The Channel Physiology of the Skin _________________________________________________________________________________ REVISION The Channel Physiology of the Skin Attila Oláh, Attila Gábor Szöllősi, and Tamás Bíró DE-MTA “Lendület” Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Debrecen, Hungary Correspondence to: Tamás Bíró MD, PhD, DSc DE-MTA “Lendület” Cellular Physiology Research Group, Department of Physiology University of Debrecen, Medical and Health Science Center Research Center for Molecular Medicine Nagyerdei krt. 98. H-4032 Debrecen, Hungary email: [email protected]; [email protected] 1 Oláh, Szöllősi, Bíró The Channel Physiology of the Skin _________________________________________________________________________________ Table of contents 1 Abstract ......................................................................................................... 5 2 The skin and its key functions ....................................................................... 6 2.1 The functional anatomy of the skin ................................................................ 6 2.2 Key functions of the skin ................................................................................ 6 2.2.1 Barrier functions ............................................................................................ 7 2.2.1.1 The physical-chemical barrier .................................................................... 7 2.2.1.2 The (micro)biological barrier ....................................................................... 9 2.2.1.3 The immunological barrier ........................................................................ 10 2.2.1.4 The barrier regeneration ........................................................................... 11 2.2.1.5 Related cutaneous diseases .................................................................... 12 2.2.2 Neuroendocrine functions ............................................................................ 12 2.2.3 Other functions ............................................................................................ 14 3 A short introduction of ion and non-ion selective channels .......................... 16 3.1 Ion channels ................................................................................................ 16 3.1.1 Voltage-gated ion channels ......................................................................... 16 3.1.2 Ligand-gated ion channels .......................................................................... 17 3.1.3 Transient receptor potential ion channels .................................................... 18 3.1.4 Other ion channels ...................................................................................... 19 3.2 Non-ion selective channels .......................................................................... 19 3.2.1 Aquaporins .................................................................................................. 19 3.2.2 Connexins ................................................................................................... 19 3.2.3 Pannexins .................................................................................................... 20 4 Roles of channels in skin physiology and in certain dermatoses ................. 21 4.1 Roles of channels in epidermal physical-chemical barrier functions and barrier recovery ........................................................................................................ 21 4.1.1 Voltage-gated channels ............................................................................... 21 2+ 4.1.1.1 Voltage-gated Ca -channels ................................................................... 21 2+ + 4.1.1.2 Ca -activated K -channels ...................................................................... 22 4.1.2 Ligand-gated channels ................................................................................ 23 4.1.2.1 nAChRs .................................................................................................... 23 4.1.2.2 Ionotropic glutamate receptors ................................................................. 24 4.1.2.3 P2X receptors .......................................................................................... 25 4.1.2.4 5-HT3 receptors ....................................................................................... 26 4.1.2.5 GABAA receptors ...................................................................................... 26 4.1.2.6 Glycine receptors ..................................................................................... 26 4.1.3 TRP channels .............................................................................................. 27 4.1.3.1 TRPV1 ...................................................................................................... 27 4.1.3.2 TRPV3 and TRPV4 .................................................................................. 28 4.1.3.3 TRPV6 ...................................................................................................... 29 4.1.3.4 TRPC channels ........................................................................................ 30 4.1.3.5 TRPA1 ...................................................................................................... 30 4.1.3.6 TRPM channels ........................................................................................ 31 4.1.4 Non-ion selective channels .......................................................................... 32 4.1.4.1 Aquaporins ............................................................................................... 32 4.1.4.2 Connexins ................................................................................................ 33 4.1.4.3 Pannexins ................................................................................................ 33 2 Oláh, Szöllősi, Bíró The Channel Physiology of the Skin _________________________________________________________________________________ 4.1.5 The complex “channel” regulation of the epidermal barrier – Controversies, explanations, theories ............................................................................................... 33 4.2 Roles of channels in wound healing ............................................................ 36 4.2.1 Voltage-gated channels ............................................................................... 36 2+ + 4.2.1.1 Voltage-gated and Ca -activated K -channels ........................................ 36 4.2.2 Ligand-gated channels ................................................................................ 36 4.2.2.1 nAChRs .................................................................................................... 36 4.2.2.2 GABAA receptors ...................................................................................... 37 4.2.3 TRP channels .............................................................................................. 37 4.2.3.1 TRPV1 ...................................................................................................... 38 4.2.3.2 TRPV3 ...................................................................................................... 38 4.2.4 Non-ion selective channels .......................................................................... 39 4.2.4.1 Aquaporins ............................................................................................... 39 4.2.4.2 Connexins ................................................................................................ 39 4.3 Roles of channels in cutaneous immune functions and in the “formation” of the immunological barrier ......................................................................................... 39 4.3.1 Voltage-gated channels ............................................................................... 39 4.3.2 Ligand-gated channels ................................................................................ 40 4.3.2.1 nAChRs .................................................................................................... 40 4.3.2.2 P2X receptors .......................................................................................... 40 4.3.2.3 GABAA receptors ...................................................................................... 42 4.3.3 TRP channels .............................................................................................. 42 4.3.3.1 TRPV1 ...................................................................................................... 43 4.3.3.2 TRPV3 ...................................................................................................... 44 4.3.3.3 TRPA1 ...................................................................................................... 44 4.3.4 Non-ion selective channels .......................................................................... 45 4.3.4.1 Aquaporins ............................................................................................... 45 4.4 “Sensory roles” of epidermal keratinocytes ................................................. 45 4.4.1 Voltage-gated ion channels ......................................................................... 45 + 4.4.1.1 Voltage-gated Na -channels .................................................................... 45 + 4.4.1.2 Two-pore K channels (K2P) ....................................................................