Contrasting Effects of Cd2+ and Co2+ on the Blocking/Unblocking of Human Cav3 Channels

Contrasting Effects of Cd2+ and Co2+ on the Blocking/Unblocking of Human Cav3 Channels Inorganic ions have been used widely to investigate biophysical properties of high voltage-activated calcium channels (HVA: Cav1 and Cav2 families). In contrast, such information regarding low voltage-activated calcium channels (LVA: Cav3 family) is less documented. We have studied the blocking effect of Cd2+, Co2+ and Ni2+ on T-currents expressed by human Cav3 channels: Cav3.1, Cav3.2, and Cav3.3. With the use of the whole-cell configuration of the patch-clamp technique, we have recorded Ca2+ (2 mM) currents from HEK−293 cells stably expressing recombinant T-type channels. Cd2+ and Co2+ block was 2- to 3-fold more potent for Cav3.2 channels (EC 50 = 65 and 122 μM, respectively) than for the other two LVA channel family members. Current-voltage relationships indicate that Co2+ and Ni2+ shift the voltage dependence of Cav3.1 and Cav3.3 channels activation to more positive potentials. Interestingly, block of those two Cav3 channels by Co2+ and Ni2+ was drastically increased at extreme negative voltages; in contrast, block due to Cd2+ was significantly decreased. This unblocking effect was slightly voltage-dependent. Tail-current analysis reveals a differential effect of Cd2+ on Cav3.3 channels, which can not close while the pore is occupied with this metal cation. The results suggest that metal cations affect differentially T-type channel activity by a mechanism involving the ionic radii of inorganic ions and structural characteristics of the channels pore. The Journal of Membrane Biology Springer Journals

Contrasting Effects of Cd2+ and Co2+ on the Blocking/Unblocking of Human Cav3 Channels

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Copyright © 2005 by Springer Science+Business Media, Inc.
Life Sciences; Human Physiology; Biochemistry, general
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