Tetrodotoxin-sensitive Ca2+ and Ba2+ currents in human atrial cells.
A tetrodotoxin (TTX)-sensitive fast inward Ca2+ current (ICa,TTX) was recorded at physiological Ca2+ levels (2 mM) in human single atrial cells. The whole-cell patch-clamp method and Na(+)-free solutions (20-22 degrees C) were used. ICa,TTX depended upon extracellular Ca2+. It was prominent at rather negative test potentials (maximal peak amplitude at approximately -40 mV) and was observed only at holding potentials lower than -80 mV. It had the same size and kinetics when Ca2+ was exchanged for Ba2+ as the charge carrier. Its rapid activation and inactivation kinetics, voltage-dependent availability and fast recovery from inactivation resembled that of the Na+ currents (INa). ICa,TTX was insensitive to 250 microM Ni2+ and 10 microM La3+, both known to block totally T-type ICa (not evidenced here). ICa,TTX was suppressed by Na+ channel inhibitors such as TTX (10 microM) and Cd2+ (20 microM) and its decay was slowed by the specific Na+ channel activator veratrine (200 micrograms/ml). We found that both time to peak and time-constant of inactivation of ICa,TTX were slower than that of INa. There was no correlation between the presence and size of ICa,TTX and that of INa. In conclusion, ICa,TTX may reflect the presence and activation of either Ca(2+)-conducting channels related to Na+ channels or, alternatively, of a fraction of Na+ channels with an increased permeability for Ca2+ and Ba2+ ions.
Lemaire
S
S
Centre de Recherches de Biochimie Macromoléculaire, CNRS, UPR 9008, INSERM U 249, Montpellier, France.
Piot
C
C
Seguin
J
J
Nargeot
J
J
Richard
S
S
D016275:Atrial Function; D001464:Barium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials; D012964:Sodium / Q000737:chemistry; D013779:Tetrodotoxin / Q000494:pharmacology*
D015220:Calcium Channels; D007473:Ion Channels; D001464:Barium; D013779:Tetrodotoxin; D012964:Sodium