We employed whole cell patch-clamp recordings to establish the effect of Zn2+ on the gating the brain specific, T-type channel isoform CaV3.3 expressed in HEK-293 cells. Zn2+ (300 µM) modified the gating kinetics of this channel without influencing its steady-state properties. When inward Ca2+ currents were elicited by step depolarizations at voltages above the threshold for channel opening, current inactivation was significantly slowed down while current activation was moderately affected. In addition, Zn2+ slowed down channel deactivation but channel recovery from inactivation was only modestly changed. Zn2+ also decreased whole cell Ca2+ permeability to 45% of control values. In the presence of Zn2+, Ca2+ currents evoked by mock action potentials were more persistent than in its absence. Furthermore, computer simulation of action potential generation in thalamic reticular cells performed to model the gating effect of Zn2+ on T-type channels (while leaving the kinetic parameters of voltage-gated Na+ and K+ unchanged) revealed that Zn2+ increased the frequency and the duration of burst firing, which is known to depend on T-type channel activity. In line with this finding, we discovered that chelation of endogenous Zn2+ decreased the frequency of occurrence of ictal-like epileptiform discharges in rat thalamocortical slices perfused with medium containing the convulsant 4-aminopyridine (50 µM). These data demonstrate that Zn2+ modulates CaV3.3 channel gating thus leading to increased neuronal excitability. We also propose that endogenous Zn2+ may have a role in controlling thalamocortical oscillations.

Zn(2+) slows down Ca(V)3.3 gating kinetics: implications for thalamocortical activity / Cataldi, Mauro; Lariccia, Vincenzo; V., Marzaioli; A., Cavaccini; G., Curia; Viggiano, Davide; L. M., Canzoniero; DI RENZO, GIANFRANCO MARIA LUIGI; M., Avoli; Annunziato, Lucio. - In: JOURNAL OF NEUROPHYSIOLOGY. - ISSN 0022-3077. - STAMPA. - 98:4(2007), pp. 2274-2284. [17699699]

Zn(2+) slows down Ca(V)3.3 gating kinetics: implications for thalamocortical activity.

CATALDI, MAURO;LARICCIA, Vincenzo;VIGGIANO, DAVIDE;DI RENZO, GIANFRANCO MARIA LUIGI;ANNUNZIATO, LUCIO
2007

Abstract

We employed whole cell patch-clamp recordings to establish the effect of Zn2+ on the gating the brain specific, T-type channel isoform CaV3.3 expressed in HEK-293 cells. Zn2+ (300 µM) modified the gating kinetics of this channel without influencing its steady-state properties. When inward Ca2+ currents were elicited by step depolarizations at voltages above the threshold for channel opening, current inactivation was significantly slowed down while current activation was moderately affected. In addition, Zn2+ slowed down channel deactivation but channel recovery from inactivation was only modestly changed. Zn2+ also decreased whole cell Ca2+ permeability to 45% of control values. In the presence of Zn2+, Ca2+ currents evoked by mock action potentials were more persistent than in its absence. Furthermore, computer simulation of action potential generation in thalamic reticular cells performed to model the gating effect of Zn2+ on T-type channels (while leaving the kinetic parameters of voltage-gated Na+ and K+ unchanged) revealed that Zn2+ increased the frequency and the duration of burst firing, which is known to depend on T-type channel activity. In line with this finding, we discovered that chelation of endogenous Zn2+ decreased the frequency of occurrence of ictal-like epileptiform discharges in rat thalamocortical slices perfused with medium containing the convulsant 4-aminopyridine (50 µM). These data demonstrate that Zn2+ modulates CaV3.3 channel gating thus leading to increased neuronal excitability. We also propose that endogenous Zn2+ may have a role in controlling thalamocortical oscillations.
2007
Zn(2+) slows down Ca(V)3.3 gating kinetics: implications for thalamocortical activity / Cataldi, Mauro; Lariccia, Vincenzo; V., Marzaioli; A., Cavaccini; G., Curia; Viggiano, Davide; L. M., Canzoniero; DI RENZO, GIANFRANCO MARIA LUIGI; M., Avoli; Annunziato, Lucio. - In: JOURNAL OF NEUROPHYSIOLOGY. - ISSN 0022-3077. - STAMPA. - 98:4(2007), pp. 2274-2284. [17699699]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/334095
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