15 Firing Mechanisms - KCa PDF

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Some neuronal ionic currents

IKCa (IC, IAHP)


Activation of BK channels
depends on both V and
[Ca2+]in
Neuronal KCa channels are colocalized with HVA CaV channels, and
are activated as a consequence of opening of the specific CaV2 or
CaV1 channels with which they are colocalized.
HVA Ca2+ channels (L-, P/Q-, N-, R-type): CaV1, CaV2

DHP drugs CaV 1.1, CaV1.2,


L-type
(Nimodipine) CaV1.3, CaV1.4

w-Aga-IVA P/Q-type CaV 2.1


(w-CTx
MVIIC)

w-CgTx GVIA N-type CaV 2.2

SNX 482 R-type CaV 2.3


HVA Ca2+ channels (L-, N-, P/Q-, R-type): CaV1, CaV2

Activation threshold: > -40 mV


Different biophysical properties depending on channel subtype, including
different kinetics of activation and inactivation, which however are slower than
those of LVA Ca2+ channels (CaV3)

CaV1 and CaV2 channels activate more slowly than NaV channels and
contribute very little (or not at all) to the upstroke phase of the AP.
They usually start to activate close to the peak of the AP and the ICa
carried by CaV1 and CaV2 channels is maximal during the
repolarization phase of the AP.
Ca current measured in an
action clamp experiment
In the terminal of the squid giant
synapse
BK channels contribute to AP repolarization, in particular
to the last phase of the repolarization, and to the AHP

In neurons expressing many BK channels, also the


inhibition of the CaV channels to which they are coupled can
lead to a prolongation of the AP if the net current after
opening of the CaV channels is outward (as in the
suprachiasmatic nucleus neuron of the figure)
BK

SK
SK channels mediate the slow AHP (lasting hundreds of ms) and the adaptation
of the frequency of APs in certain neurons (e.g. cortical pyramidal cells)

The slow AHP in cortical


pyramidal neurons is due to the
high expression of SK
channels, whose deactivation
kinetics reflect the decay of
intracellular [Ca2+]in.
Cf complete elimination of the
slow AHP when the
extracellular [Ca2+] is lowered
to 0.2 mM, thus eliminating Ca
influx through CaV channels
and hence activation of SK
channels

The frequency adaptation


during a train of APs in
cortical pyramidal neurons
is due to the high
expression of SK channels
and the prolonged AHP that
they mediate.
CF complete elimination of
the AP frequency
adaptation in the presence
of Cd2+ which blocks the
HVA CaV channels
BK

SK

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