Ion Channels

Learning Objectives
Active and Passive Transport of Ions KcsA and mechanisms of ion permeation Ligand-gated Ion Channels Voltage-gated Ion Channels Blockers of Ion channels

Ion Carriers and Ion Channels

Fig. 10-1

Valinomycin
Fig. 10-2 Fig. 10-3

Gramicidin A
Fig. 10-5

KcsA, a Bacterial

+ K

channel

Fig. 10-7

The Permeation Pathway

Fig. 10-7B

The Mechanism of Ion Permeation

Fig. 10-7C Fig. 10-8

Nicotinic Acetylcholine Receptor

http://www.chm.bris.ac.uk/org/gallagher/nAChR.gif

Ligand-Gated Ion Channels

Example: nicotinic acetylcholine receptor. Agonist: acetylcholine. Antagonists: bungarotoxin, tubocurarine, myorelaxants
Side View Agonist binding site Top View

One subunit has 4 transmembrane helices

Receptor contains 5 pseudosymmetric subunits

Bungarotoxin

IVCHTTATSP ISAVTCPPGE NLCYRKMWCD AFCSSRGKVV ELGCAATCPS KKPYEEVTCC STDKCNPHPK QRPG

Tubocurarine
d-tubocurarine is one of the active components of the arrow poison (curare) of South American Indians.

Iban tribesman, former headhunters, positions to shoot poison dart. Skrang River, Sarawak, Borneo (Malaysia)

Voltage-Gated Ion Channels

Top View

+ + +

+
Voltage sensor

Voltage-gated K+ channels consist of four identical subunits, each subunit having six transmembrane segments.

+ + +

+ + +

+ + +

+ + +

Na+ channels. Blockers: tertodotoxin, local anesthetics Ca2+ channels. Blockers: cardiovascular drugs, conotoxins

Tetrodotoxin, a Blocker of Na+ Channel

The word "tetrodotoxin" is derived from the order of fish, tetraodontidae, which means "four-toothed".

Puffer fish is among the most poisonous of all marine life. It inhabit the shallow waters in tropical zones. The liver, gonads, intestines, and skin of these fish contain tetrodotoxin that can cause death in approximately 60% of persons who ingest it.

Poison-Arrow Frogs

Dendrobatids are also known as poison-arrow (arrow-poison, dart-poison frogs). Dendrobatids are about 20 to 40 mm in length. Many dendrobatids are brightly colored (and poisonous). However, there are many dull-colored species that do not appear to be poisonous. Indians in Colombia rub their blowgun darts onto the backs of Phyllobates terribilis to load the darts with poison.

Batrachotoxin, Na+ channel Agonist

Batrachotoxin, first isolated from Dendrobates pumilo, is one of a group of potent lipid- soluble neurotoxins which binds voltage-gated Na+ channels.

Dendrobates lehmani

Batrachotoxin is the most powerful animal venom known, being 250 times more powerful than strychnine.

Phyllobates terribilus

Batrachotoxin is present in extreme amounts in Phyllobates terribilus GOLDEN POISON DART FROG, (Phyllobates terribilis), COLOMBIA

Local Anesthetics

Lidocaine

Phenytoin

Local anesthetics block voltage-gated Na+ channels