Looking for a Tutor Near You?

Post Learning Requirement »
x

Choose Country Code

x

Direction

x

Ask a Question

x

x
x
For better view click here
x
Hire a Tutor
DISCOVER

Ion Channels

Loading...

Published in: Biology | Physiology | Science
3,332 Views

This PPT contains description in brief about potassium ion channel of two-pore domain type.

Sourajit M / Bangalore

2 years of teaching experience

Qualification: Ph.D (Indian institute of science Bangalore - 2015)

Teaches: Bio Technology, Biology, Chemistry, EVS, Physiology, Zoology, Mathematics, Physics, Bengali, Microbiology

Contact this Tutor
  1. Much more than a leak : revisiting different aspects of K2P channels + Brief history about K2P channels + Do K2P channels : display voltage-dependent gating ??? contribute to action potential generation ??? + Functional role of Alternative Splicing and Alternative Translation Initiation
  2. Characteristics of ?2? channels Pore domains Extracellular Phylogeny of ?2? channels ? ? lntracellular c (Enyedi & 2010) Assemble ?? dimers Two pore forming loops Four transmembrane helices + Distribution: CNS, Heart, Blood vessels, Kidney & others ????? TREK TASK ???? : TRESK ???-? 37% ????-7 kCNk7, ?????-2 kCNk6, kCNk12, ?.??12? ????.2 ????.1 ????13, kCNk4, ? 2?4.1 TRAAK - KCNK2, ????-? TREk-2 kCNK10, ?2?10.1 kCNk3. TASK-1 54% TASK.3 kCNk15, ?2?15? KCNK17, ? ???-?-2 (TASK-4) TASk.2 kCNk5, ????.? ????16, kCNk18k ?? ? TRESK•1 Weak inward rectification lnhibited by halothane Lipid, temperature and stretch activated lnhibited by extracellular protons ?? -65-75) lnhibjted by extracellular protons Calc;um activated (Bayliss and Barrett, 2008)
  3. History of the eukaryotic K2P channels' clades
  4. J. GEN. PHYSIOLw @ ne R(kkefeller University Volume 100 December 1992 1021-1040 A Mechanosensitive K + Channel in Heart Cells Activation DONCHEE KIM Acid From the Dqartment of Physiology and Bophysics, Chicago Medical Schq»li Nonh Chicago, Ilinois 60064 (mmHg) + 60 + 20 ill i (2.2) (3.7) 96 (14.8) (22.1) 100 ms 1.0 10 Pressure (mmHg)
  5. A TEA-Insensitive Flickering Potassium Channel Active around the Resting Potential in Myelinated Nerve J. Membrane Biol. 130, 149-162 (1992 Duk-Su Koh, Peter Jonast, Michael E. Bräu, and Werner Vogel TEA Ba + TEA control control C; + TEA 200 ms 2 s B Fig. 1. Typical activity of the flicker channel at different time scales and different resolutions. Outside-out patch. Bath: 105 mM-Ko, pipette: 105 mM-Ki. Membrane potential Em 90 m V, filter frequency: 1 kHz (A, B) and 10 kHz (C). -90 mV TEA Ba + TEA control -60 mV 10 PA 20 s + TEA control
  6. mammalian two pore domain mechano-gated -like K channel The No.15 pp.4283-4290, 0.5 TREK-I ' Amanda J.Patel, Eric Honoré. Franeois Maingret. Florian Lesage, Michel Fink. Fabrice Duprat and Michel Lazdunskil I / I max 2.4 1.2 -50 -1.2 CHCI 3 control 50 100 o -40 -80 P (mm Hg) Stretch genera anes e IC I (nA) control 1 0.8 0.6 0.4 -100 -50 2 1 -100 -50 -2 IOpMAA control 50 100 V (mV) CPZ (W M) 2 min cAMp + AA cAMP 50 100 0.1 1 CHCI 3 V (mV) cAMP addition 10 mM AA Cationic Amphipaths
  7. Are K2P channels leak channels...??? K2P channels are described as : + 'Leak Channels' + 'Background Channels' + 'Open Rectifier Channels' (Goldstein et al., 2001) (Honoré, 2007) (Goldstein et al., 2001) Outward rectification in TASK channels What is an 'ion-selective leak channel' ? Assumptions of crystal-field theory + Linear voltage gradient + Independent movement of ions across membranes Current-Voltage relationship of K + channels: + Strong outward rectification in physiological conditions + Linear in symmetrical K + concentrations -150 5K 22K 55K 05K 55K 2 50 -2 -4 (Duprat et al., 1997)
  8. Surprisingly... !!! Properties incompatible with the concept of 'open rectifier' or 'K + selective holes' p 2 mTASK-l 1 mTBAK-l -IOO -50 -2 NPo 0.2 0.1 50 IOOmV -80 -40 0 40 80 Inward rectification with symmetrical K + gradient Increase in open probability with depolarisation (Kim et al., 1999)
  9. Do K2P channels show time-dependent gating ??? 1.0 c 0.4 02 0.0 : 20 ms TREK-I a t -19 ms decay t 210 ms decay + K2P channels are not permanently open + Open probability increases with depolarisation + Time-dependent gating is observed Upon depolarisation, an instantaneous component followed by a time- dependant component Upon repolarisation, pronounced deactivation tail is observed Is regulatory K + channel a better nomenclature for K2P channels?
  10. TASK-3 KO urrent injetion 20 PA o eo frequency unnn 20 rnV 200 ms Wild-type n = 16 In s aping action potentla pattern an 24 PA 28 PA 1.0 0.3 0.6 0.4 on O 32 PA 36 PA n = 10 44 PA 48 PA 3 120 100 60 TASK-3 KO 0 4 8 12 '16 m 24 28 32 40 44 48 Current injection (PA) 4 8 12 16 20 24 28 32 36 40 Current injection above threshold (PA) (Brickley et al., 2007)
  11. Regulation of the number of K2P channels on the cell surface Alternative splicing Enn I DNA Eiff I RNA 2 3 mRNA Translation Protein A Exon 2 Exon 2 Exon 3 Exon 3 Alternative Splicing 1 2 Translation Protein B Exon4 E*tn4 Exon 5 5 3 2 Translation Protein C Alternative Translation Initiation (Wikipedia) ORF of K2P channels is encoded by 2-7 exons TASK-I : 2 exons, TREK clade: 7 exons Conserved splice site: G Y/ / G Differential expression of N-terminal splice in various tissues - significance?
  12. Pflu eßArch-EurJPh siol 2014 466:1559-1570 (Rinné S et al., 2014) A splice variant of the two-pore domain potassium channel TREK-I with only one pore domain reduces the surface expression of full-length TREK-I channels rTUK-1 Exon 5 Exon 6 ..CTGACCACCATTGGATTTGGCGATTATGTGGCAGqgagg..gc4TGGGICGGAC11 . tTUK-1e Exon 4 G SDI. Exon 6 ..1AAGÆTTGCCIAAGTÆGGACICATTTATTgggag..gc41GGGTCGGACA. hNK-1 hTREK-1e Exon 5 Exon 4 Exon 6 G SDI. Exon 6 V DPI TREK-I a-d TREK-Ie 0-8 0.6 0.4 0-2 0.0 . .AAAGGAATTGCCæGTGGAAGATACGTTTATTÉgag. KGIAKVEDTFI
  13. Dominant Negative Effects of a Non-conducting TREK 1 Splice Variant Expressed in Brain Received for publication, January 29, 2010, and in revised form, June 29, 2010 Published, JBC Papers in Press, July 6, 2010, DOI 10.1074/Jbc.M11 0.108423 Emma L. Veale , Kathryn A. Rees*, Alistair Mathie*l, and Stefan Trapp 61 81 101 121 141 161 81 ACAGTCTCCACGATTTTCCTGGTGGTCGTCCTCTACCTGATCATCGGAGCCACGGTGTTC AAGGCATTGGAGCAGCCTCAGGAGATTTCCCAGAGGACCACCATTGTGATCCAGAAGCAG ACCT TCATAGCCCAGCATGCCT TAGTGGCÄGCAATAAÄCGCAGGGATTATCCCCTTÄGGAÄÄCAGCTCCAATCAAGTTAG CTGGGÄCCTCGGAAGCTCTTTCTT 'TTTGCTGGTACTGTTATCACAÄCCÄTÄ GATTT GGPAACATCTCCCCACGAACTGAAGGTGGAAAAÄTÄTTCTGCÄTCATCTATGCCTTGCTG GGAATTCCCCTCTTTGGCTTTCTACTGGCTGGGGTTGGTGATCAGCTAGGAACTATATTT 114 bp Frame shifted 'e Sequence • NH2 TREKIAEx4 stop 50 76 40 30 20 10 14 65 85 IOS 125 143 NH2 165 17 23 1:1 20 1.5 0.5 Exon 4 COOH TREKI TREKI + TREKlAEx4 TREKlAEx4 -100 -80 -60 Voltage (mV) -40 -20 DLETSHHAQKAAKYSVSSMPYWEFPSLVFSWLELEIS
  14. Alternative Translation Initiation TREK-I + 2 translation initiation sites + 2 isoforms are functional - long and short forms + Splice variant lacking exon 4 had dominant negetive effect on long isoform Significance of ATI Reported single-channel conductance in heterologous system: 95 - 130 PS (Han J et al., 2003) TREK-2 3 translation initiation sites Long isoform's conductance- 52ps Short isoform's conductance- -200 ps - 80 2 different conductance states ! 40 PS and 130 PS were reported in Native rat cardiomyocytes and heterologous system (Li XT et al., 2006)

Need a Tutor or Coaching Class?

Post an enquiry and get instant responses from qualified and experienced tutors.

Post Requirement

Related PPTs

Upload PPTs

If you have your own PowerPoint Presentations which you think can benefit others, please upload on LearnPick. For each approved PPT you will get 100 Credit Points and 100 Activity Score which will increase your profile visibility.

Upload Now
Home > PowerPoint Slides > Ion Channels