Ld. Partridge et Cf. Valenzuela, Ca2+ store-dependent potentiation of Ca2+-activated non-selective cation channels in rat hippocampal neurones in vitro, J PHYSL LON, 521(3), 1999, pp. 617-627
1. Potentiation of calcium-activated non-selective cation (CAN) channels wa
s studied in rat hippocampal neurones. CAN channels were activated by IP3-d
ependent Ca2+ release following metabotropic glutamate receptor (mGluR) sti
mulation either by Schaffer collateral input to CA1. neurones in brain slic
es in which ionotropic glutamate and GABA(A) receptors, K+ channels, and th
e Na+-Ca2+ exchanger were blocked or by application of the mGluR antagonist
ACPD in cultured hippocampal neurones.
2. The CAN channel-dependent depolarization (Delta V-CAN) was potentiated w
hen [Ca2+](i) was increased in neurones impaled with Ca2+-containing microe
lectrodes.
3. Fura-2 measurements revealed a biphasic increase in [Ca2+](i) when 200 m
u M ACPD was bath applied to cultured hippocampal neurones. This increase w
as greatly attenuated in the presence of Cd2+.
4. Thapsigargin (1 mu M) caused marked potentiation of Delta V-CAN in CA1 n
eurones in the slices and of the CAN current (I-CAN) measured in whole cell
-clamped cultured hippocampal neurones.
5. Ryanodine (20 mu M) also led to a potentiation of Delta V-CAN while neur
ones pretreated with 100 mu M dantrolene failed to show potentiation of Del
ta V-CAN when impaled with Ca2+-containing microelectrodes.
6. The mitochondrial oxidative phosphorylation uncoupler carbonyl cyanide m
-chlorophenyl hydrazone (2 mu M) also caused a potentiation of Delta V-CAN.
7. CAN channels are subject to considerable potentiation following an incre
ase in [Ca2+](i) due to Ca2+ release from IP3-sensitive, Ca2+-sensitive, or
mitochondrial Ca2+ stores. This I-CAN potentiation may play a crucial role
in the 'amplification' phase of excitotoxicity.