Set firing properties (such
as how many spikes) and
action potential threshold
Action potential time-course (duration)
Increasing K channel
conductance shortans AP
length
Decreasing K Channel
conductance lengthens AP
Would not work without
Sodium channels and the Na/K
ATPase Pump
Neuronal Excitation and Ion
Concentrations
Resting potential
around -60 mV
Action potential (Depolarisation)
Threshold potential up to around +45mV
AP shape depends on Na+ K+ balance
Refractory Period
Hyperpolarisation
mV below resting potential
Repolarisation
point where mV begins to drop after action potential
No further excitation, even at increasing intensities of stimuli
Ion concentrations
Intracellular
Extracellular
K+ 4.5mM
Na+ 145mM
Ca2+ 1.2mM
Cl- 116mM
K+ 120 mM
Na+ 15mM
Ca2+ 0.0001mM
Cl- 20mM
Antagonists
TEA
will block most K+ channels at 10-100mM, but at 1 mM it is
relatively specific for Kv3 (and BK channels)
Dtx
specifically blocks Kv1 channels
Kv1 Active at Depolarisation. Increased
conductance in Kv1 will increase threshold
potential. Kv3 active at peak mV and during
repolarisation. Increase conductance
shortens AP
Reversal Potential
-88mV
+60mV
+130mV
-61mV
K+ Channel Families
Leak Channels
2 Families
Inward Rectifiers
2 Transmembrane domains
Oldest in evolutionary terms
then elaborated upon
e.g. KcsA
Tandem pore, outward rectifiers
4 TM
KCNK channel family
subject to strict regulation by
second messenger systems
Set resting membrane potential
Gated channeld
Ligand-gated
3 Families
Voltage Gated
3 Famlies
Kv1-Kv4
Delayed Rectifiers
Kv5-Kv9
Accessory subunits
Kv10-Kv12
Heart
Repolarizing AP and controlling excitability
Most recent in evolution
6 TM
Kv Channel Structure
Homotetramer
Kva and KvB subunits
four alpha-subunits, which span the cell membrane
four beta-subunits that lie just inside the membrane
Kva
6 transmembrane alpha helices
TM regions 1-4 form the voltage-sensing region
TM 4 has has positively charged
residues of arginines and lysines to
detect transmembrane voltage changes
Selectivity sequence
TVGYG
Allows K+ conductance only
Tetramerisation occurs
at N-terminal
C-terminal used in
phosphorylation and regulation
N-Terminal domain acts as a 'ball
and chain' plug in inactivation
For inactivation to occur, a positively charged inactivation particle
(ball) has to pass through one of the lateral windows and bind in the
hydrophobic binding pocket of the pore's central cavity. This blocks
the flow of potassium ions through the pore. There are four balls
and chains to each channel, but only one is needed for inactivation.