Chapter 10 Membrane Channels S E C T I O N III Copyright 2008 by Saunders/Elsevier. All rights reserved. Illustrations by Graham Johnson Cell Biology, 2e Thomas D. Pollard William C. Earnshaw with Jennifer Lippincott-Schwartz José A. Cardé-Serrano, PhD Biol 4018 – Celular-Molecular Universidad de Puerto Rico, Aguadilla

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.

Epithelial transport Membrane excitability Signaling Functions of membrane channels Fig Copyright 2008 by Saunders/Elsevier. All rights reserved.

Historic events in channel biology 1950’sMicroelectrode studies lead to channel concept 1970’sFirst channel proteins purified 1980’sChannel genes and cDNAs cloned diversity enormous properties manipulated by mutagenesis Single channel recordings conformational states identified 1990’sFirst channel structures Copyright 2008 by Saunders/Elsevier. All rights reserved.

Single channel recording with a patch clamp electrode Figs & Copyright 2008 by Saunders/Elsevier. All rights reserved.

Measurement of membrane potential with a microelectrode Fig 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 Fig Copyright 2008 by Saunders/Elsevier. All rights reserved.

S5-S6 family of ion channels Fig Copyright 2008 by Saunders/Elsevier. All rights reserved.

Six other families of channels Fig Copyright 2008 by Saunders/Elsevier. All rights reserved.

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

Fig Copyright 2008 by Saunders/Elsevier. All rights reserved.

Activity states of ion channels Fig Structures of K-channels with open & closed gates Copyright 2008 by Saunders/Elsevier. All rights reserved. Abiertos Cerrados Inactivados

Single channel recording with a patch clamp electrode Figs & 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

Fig TRP family Na + /Ca 2+ channels are activated by temperature and extracellular chemicals Copyright 2008 by Saunders/Elsevier. All rights reserved.

Cyclic nucleotide-gated channels are Na + /Ca 2+ channels gated by cAMP or cGMP binding to a cytoplasmic domain Ca 2+ -gated K + channels Channels gated by intracellular ligands Fig 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

Permeability: Na + /K + >Ca 2+ Na + /K + Cl - Amonia Rh Extracellular ligand-gated ion channels Fig Acetylcholine receptor Copyright 2008 by Saunders/Elsevier. All rights reserved.

Crystal structure of an ammonium channel: ion channels selective for a gas: NH 3 ! Famous in medicine as the Rh antigen responsible for immune incompatibility between Rh - mothers and Rh + fetuses Fig Copyright 2008 by Saunders/Elsevier. All rights reserved.

Aquaporin water channel Fig Copyright 2008 by Saunders/Elsevier. All rights reserved.

¿Preguntas?