Biomedical Engineering Reference
In-Depth Information
13
Ion Channels: Structure
and Function
Søren-Peter Olesen and Daniel B. Timmermann
CONTENTS
13.1 Introduction ......................................................................................................................... 207
13.1.1 Ion Channels Are Pores through the Cell Membrane............................................ 208
13.1.2 Ion Currents Change the Electrical Membrane Potential...................................... 208
13.1.3 Gating of Ion Channels ..........................................................................................209
13.1.4 Molecular Structures of Ion Channels ................................................................... 211
13.1.5 Ion Channels and Disease ...................................................................................... 211
13.1.6 Physiological and Pharmacological Modulation of Ion Channels ......................... 211
13.1.7 Drug Screening on Ion Channels........................................................................... 211
13.1.8 Structure of Voltage-Gated Ion Channels.............................................................. 212
13.2 Physiology and Pharmacology of Voltage-Gated Ion Channels—Potassium Channels .... 213
13.3 Voltage-Gated Calcium Channels....................................................................................... 215
13.3.1 Structure and Molecular Biology........................................................................... 215
13.3.2 Physiological Roles of Voltage-Gated Calcium Channels ..................................... 217
13.3.3 Pharmacology of Voltage-Gated Calcium Channels ............................................. 217
13.3.3.1 Ca
v
1-Family (L-Type Currents) .............................................................. 218
13.3.3.2 Ca
v
2-Family (N-, P/Q-, and R-Type Current)......................................... 220
13.3.3.3 Ca
v
3-Family (T-Type Current) ............................................................... 220
13.3.3.4 Auxiliary Subunits ................................................................................. 220
13.4 Voltage-Gated Sodium Channels........................................................................................ 221
13.4.1 Structure and Molecular Biology of Voltage-Gated Sodium Channels................. 221
13.4.2 Physiological Roles of Voltage-Gated Sodium Channels ...................................... 221
13.4.3 Pharmacology of Voltage-Gated Sodium Channels .............................................. 222
13.5 Chloride Channels............................................................................................................... 222
13.6 Ligand-Gated Ion Channels ................................................................................................ 223
Further Readings............................................................................................................................ 223
13.1 INTRODUCTION
Ion channels form pores through the cell membrane, which are permeable to the small physiologi-
cal ions Na
+
, K
+
, Ca
2
+
, and Cl
−
. The channels can open and close and thereby turn the l ux of the
charged ions through the cell membrane on and off. By this mechanism, the ion channels govern
the fast electrical activity of the cells. Additionally, ion channels control Ca
2
+
inl ux and regulate
responses as diverse as muscle contraction, neuronal signaling, hormone secretion, cell division,
and gene expression. The opening of the channels is subject to regulation by physiological stimuli
such as changes in membrane potential and ligand binding. Ion channels also lend themselves to
207
