Download Estructuración de los Canales Membranales

SECTION
III
Cell Biology, 2e
Thomas D. Pollard
William C. Earnshaw
with Jennifer Lippincott-Schwartz
Chapter 10
Membrane Channels
Illustrations by Graham Johnson
José A. Cardé-Serrano, PhD
Biol 4018 – Celular-Molecular
Universidad de Puerto Rico,
Aguadilla
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Objetivos
• Al finalizar el estudiante podrá:
– Definir lo que es una proteína membranal tipo canal.
– Conocer la estructura de los canales.
– Conocer las propiedades básicas de ésta proteína que
le permiten realizar su labor.
– Clasificar las diferentes tipos de canales.
– Mencionar y explicar el mecanismo de acción de los
canales membranales.
– Comparar y contrastar los diversos tipos de canales
membranales.
Three classes of membrane transport proteins
Fig. 8-1
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Functions of membrane channels
Membrane
excitability
Epithelial
transport
Signaling
Fig. 10-1
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Historic events in channel biology
1950’s
Microelectrode studies lead to channel concept
1970’s
First channel proteins purified
1980’s
Channel genes and cDNAs cloned
• diversity enormous
• properties manipulated by mutagenesis
Single channel recordings
• conformational states identified
1990’s
First channel structures
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Single channel recording with a patch clamp electrode
Figs. 10-4
& 10-16
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Measurement of membrane potential with a microelectrode
Fig. 10-16
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Estructuración de los Canales Membranales
• Proteínas integrales
• Mayoría son multisubunidades (2-6) polipeptídicas.
• 2 o mas hélice alfa segmentos transmembranales
– Hidrofóbicos
– 1, 2 o más.
– Porina: excepción (Placas ß)
• Activos en forma de monómeros.
Clasificación
•
•
•
•
•
•
•
De acuerdo a la estructura primaria. ++
De acuerdo al ion que transportan.+De acuerdo al modo de regulación.+De acuerdo al rol fisiológico.+Sensitividad a drogas +Tabla 10-1 asignada -Bloqueadores
Figura 10-2 asignada
Classification of
channels based on
structure and
evolution
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Fig. 10-2
S5-S6 family of ion channels
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Fig. 10-2
Six other families of channels
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Fig. 10-2
Estructuración de los Canales Membranales
• Transportadores de K+
• Poseen dos segmentos
transmembranales.
– alfa hélice,
conectados mediante
un lazo P.
• Segmentos hidrofóbicos
cercanos en el extremo
citoplasmático;unidos, más
separados en el
extracelular.
• Posee secuencia conservada
: GYG .
KcsA K-channel with 2 transmembrane helices & a P-loop
KcsA K-channel with 2 transmembrane helices & a P-loop
Fig. 10-3
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Activity states of ion channels
Abiertos
Cerrados
Inactivados
Fig. 10-5
Structures of K-channels
with open & closed gates
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Single channel recording with a patch clamp electrode
Figs. 10-4
& 10-16
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Estructuración de un
Canal regulado por
voltaje
- Producción potenciales
de acción
- Transducción de
señales eléctricas a
químicas (Ca+2)
- HERG- K+
- Na+ - anestesia
- Lidocaina para el
corazon?
- Ca+2
- Tabla 102
TRP family Na+/Ca2+ channels are activated
by temperature and extracellular chemicals
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Fig. 10-9
Channels gated by intracellular ligands
• Cyclic nucleotide-gated
channels are Na+/Ca2+
channels gated by cAMP
or cGMP binding to a
cytoplasmic domain
• Ca2+-gated K+ channels
Fig. 10-10
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Ion Channels Gated by Extracellular Ligands
Glutamate receptors: (asignado)
K+/Na+ channels gated by glutamate binding to the
extracellular domain
Nicotinic Acetylcholine Receptor
-Exitador para cationes en el sarcolema
-Potencial de acción contracción muscular
-Reconoce la nicotina, en el SNC= adicción
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Fig. 10-11
Extracellular ligand-gated ion channels
Permeability:
Na+/K+>Ca2+
Na+/K+
ClAmonia
Rh
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Acetylcholine receptor
Fig. 10-12
Crystal structure of an ammonium channel:
ion channels selective for a gas: NH3!
Fig. 10-14
Famous in medicine as the Rh antigen responsible for immune
incompatibility between Rh- mothers and Rh+ fetuses
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Aquaporin water channel
Fig. 10-15
Copyright 2008 by Saunders/Elsevier. All rights reserved.
¿Preguntas?