Monovalent cations contribute to T-type calcium channel (Cav3.1 and Cav3.2) selectivity

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9 Scopus citations

Abstract

Low voltage-activated (LVA) Ca2+ channels regulate chemical signaling by their ability to select for Ca2+. Whereas Ca 2+ is the main permeating species through Ca2+ channels, Ca2+ permeation may be modified by abundant intra- and extracellular monovalent cations. Therefore, we explored monovalent cation regulation of LVA Ca2+ permeation in the cloned T-type Ca2+ channels α1G (Cav3.1) and α1H (Cav3.2). In physiological [Ca2+], the reversal potential in symmetrical Li + was 19 mV in α1G and 18 mV in α1H, in symmetrical Cs+ the reversal potential was 36 mV in α1G and 37 mV in α1H, and in the bi-ionic condition with Li+ in the bath and Cs+ in the pipette, the reversal potential was 46 mV in both α1G and α1H. When Cs+ was used in the pipette, replacement of external Cs+ with Li+ (or Na+) shifted the reversal potential positive by 5-6 mV and increased the net inward current in α1G. Taken together the data indicate that in physiological [Ca2+], external Li+ (or Na+) permeates more readily than external Cs+, resulting in a positive shift of the reversal potential. We conclude that external monovalent cations dictate T-type Ca2+ channel selectivity by permeating through the channel. Similar to Li+, we previously reported that external [H+] can regulate T-type Ca2+ channel selectivity. α1H's selectivity was more sensitive to external pH changes compared to α1G. When Cs + was used in the pipette and Li+ was used in the bath external acidification from pHo 7.4 to 6.0 caused a negative shift of the reversal by 8 mV in α1H. Replacement of internal Cs+ with Li+ reduced the pH-induced shift of the reversal potential to 2 mV. We conclude that, similar to other external monovalent cations, H + can modify T-type Ca2+ channel selectivity. However, in contrast to external monovalent ions that readily permeate, H+ regulate T-type Ca2+ channel selectivity by increasing the relative permeability of the internal monovalent cation.

Original languageEnglish
Pages (from-to)185-194
Number of pages10
JournalThe Journal of Membrane Biology
Volume193
Issue number3
DOIs
StatePublished - Jun 1 2003

Keywords

  • Calcium channel
  • Ion permeation
  • Low-voltage-activated channel
  • Patch-clamp
  • Selectivity

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

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