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

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Abstract

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 (EC50 = 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.

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Acknowledgement

We are deeply grateful to Dr. Edward Perez-Reyes (University of Virginia, Charlottesville, VA) for his enormous contribution providing cell lines stably expressing Cav3 channels, and his comments on the manuscript. This work was supported by the following grants: CONACyT (Mexico) I37976-B and J-40693-Q to J.C. Gomora, and DGAPA-UNAM (Mexico) IN201602 to J.C. Gomora.

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  1. R. Bartolo

    Present address: Facultad de Biología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, 58040, Mexico

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  1. Departamento de Biofisica, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, Mexico City, DF, 04510, Mexico

    D. Díaz, R. Bartolo, D.M. Delgadillo, F. Higueldo & J.C. Gomora

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  1. D. Díaz
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Correspondence to J.C. Gomora.

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Díaz, D., Bartolo, R., Delgadillo, D. et al. Contrasting Effects of Cd2+ and Co2+ on the Blocking/Unblocking of Human Cav3 Channels. J Membrane Biol 207, 91–105 (2005). https://doi.org/10.1007/s00232-005-0804-1

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  • DOI: https://doi.org/10.1007/s00232-005-0804-1

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