Overexpressed Ca-v beta 3 inhibits N-type (Ca(v)2.2) calcium channel currents through a hyperpolarizing shift of "ultra-slow" and "closed-state" inactivation

Yasuda, T., Lewis, R. J. and Adams, D. J. (2004) Overexpressed Ca-v beta 3 inhibits N-type (Ca(v)2.2) calcium channel currents through a hyperpolarizing shift of "ultra-slow" and "closed-state" inactivation. Journal of General Physiology, 123 4: 401-416. doi:10.1085/jgp.200308967

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Author Yasuda, T.
Lewis, R. J.
Adams, D. J.
Title Overexpressed Ca-v beta 3 inhibits N-type (Ca(v)2.2) calcium channel currents through a hyperpolarizing shift of "ultra-slow" and "closed-state" inactivation
Journal name Journal of General Physiology   Check publisher's open access policy
ISSN 0022-1295
Publication date 2004
Sub-type Article (original research)
DOI 10.1085/jgp.200308967
Open Access Status File (Publisher version)
Volume 123
Issue 4
Start page 401
End page 416
Total pages 16
Place of publication New York
Publisher Rockefeller University Press
Collection year 2004
Language eng
Subject C1
320305 Medical Biochemistry - Proteins and Peptides
730104 Nervous system and disorders
Abstract It has been shown that P auxiliary subunits increase current amplitude in voltage-dependent calcium channels. In this study, however, we found a hovel inhibitory effect of beta3 Subunit on macroscopic Ba2+ currents through recombinant N- and R-type calcium channels expressed in Xenopus oocytes. Overexpressed beta3 (12.5 ng/ cell cRNA) significantly suppressed N- and R-type, but not L-type, calcium channel currents at physiological holding potentials (HPs) of -60 and -80 mV At a HP of -80 mV, coinjection of various concentrations (0-12.5 ng) of the beta3 with Ca,.2.2alpha(1) and alpha(2)delta enhanced the maximum conductance of expressed channels at lower beta3 concentrations but at higher concentrations (>2.5 ng/cell) caused a marked inhibition. The beta3-induced Current suppression was reversed at a HP of - 120 mV, suggesting that the inhibition was voltage dependent. A high concentration of Ba-2divided by (40 mM) as a charge carrier also largely diminished the effect of P3 at -80 mV Therefore, experimental conditions (HP, divalent cation concentration, and P3 subunit concentration) approaching normal physiological conditions were critical to elucidate the full extent of this novel P3 effect. Steady-state inactivation curves revealed that N-type channels exhibited closed-state inactivation without P3, and that P3 caused an similar to40 mV negative shift of the inactivation, producing a second component with an inactivation midpoint of approximately -85 mV The inactivation of N-type channels in the presence of a high concentration (12.5 ng/cell) of P3 developed slowly and the time-dependent inactivation curve was best fit by the sum of two exponential functions with time constants of 14 s and 8.8 min at -80 mV Similar ultra-slow inactivation was observed for N-type channels Without P3. Thus, P3 can have a profound negative regulatory effect on N-type (and also R-type) calcium channels by Causing a hyperpolarizing shift of the inactivation without affecting ultra-slow and closed-state inactivation properties.
Keyword Physiology
Voltage-dependent Calcium Channel
Xenopus Oocyte
Beta 3 Auxiliary Subunit
Negative Regulation
Voltage-depenclent Inactivation
Rat Hippocampal-neurons
Dependent Ca2+ Channels
Temporal-lobe Epilepsy
Beta-subunit
Xenopus Oocytes
Alpha(1) Subunit
Functional Expression
Auxiliary Subunits
Molecular-cloning
Charge Movement
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 05:11:35 EST