Lecture 23 - Gap Junctions

Connexons

gap junctions

connexon function

provide conduits for the movement of molecules

connexon formation

arise between two connexon hemichannels from adjacent cells

3 connexins on either cell = 6 connexins in a connexon

connexins structure

4 transmembrane a-helices

N and C termini in cytoplasmic side

2 extracellular loops interact with neighbouring loops

connexin turnover

takes several hours

new connexins enter at edges

old connexins removed from center

connexon channels

cone shaped

pass hydrophilic molecules

what molecules pass through connexons

ions, peptides, secondary messengers (signalling), metabolites, ATP, RNA

Daniel Goodenough

proposed connexins in 1974

discovered Cx43 and Cx32

Cx proteins

24 proteins

21 in humans

Cx43

most ubiquitously expressed connexin

connexin connection

different combos possible

hetero/homo meric (binding)

hetero/homo typic (interacting)

different combos = diff properites

innexins

invertebrate connexins

8 protein hemichannels

structurally similar

no sequence similarites

connexon control

voltage gating

proton and calcium level gating

protein kinase gating

slow (1-3 seconds)

connexon in heart

20% open at a timen

connexon in nerves

1% open at a time

oleamide

blocks gap junctions

makes animals sleep

halothane

closes gap junctions and closes electrical currents

high \[ca\]

closes connexons

gap junction uses

synchronizing cilia beating in lungs

provides holes in bones for nutrient movement

action potentials between cardiac and smooth muscle

ODDD

Cx43 mutation (60+)

reduced/no ability to form functional gap junctions

dominant

cardiovascular connexins

Cx36, Cx40 and Cx43

no phenotype

cataracts

Cx46 and Cx50

charcot marie tooth disease

Cx32

peripheral nerve degeneration

200 mutations

loss of function (no plaques in gap junctions)

prevent Cx gating

Cx32

found in myelin surrounding nerves

hearing loss

Cx26

truncation of protein

missense mutation