Ba(2+)-induced action potentials in osteoblastic cells.
Trains of long-duration "action potentials" were induced by Ba2+ in osteoblast-like rat osteosarcoma cells (ROS 17/2.8), under current clamp and voltage clamp. Large depolarizing pulses were seen in microelectrode measurements at 37 degrees C following the addition of 10 or 20 mM Ba2+ to physiological bathing medium. Application of BAY K 8644 resulted in the onset of the pulses at earlier times and at more negative potentials. The pulses were blocked by nifedipine and Cd2+, but not by Ni2+. Large inward current pulses were seen in whole-cell patch technique voltage-clamp measurements at 37 degrees C in the presence of from 10 to 110 mM Ba2+ in the bathing medium. The current pulses were not seen at 22 degrees C in the presence of 110 mM Ba2+, but could be induced by BAY K 8644. These pulses were not blocked by TTX, but were blocked by nifedipine, Cd2+, Zn2+, Co2+, and by an increase in bathing [Ca2+]. The shape and frequency of the current pulses were the same as for voltage pulses under current clamp. A model that can explain these observations involves opening of L-type Ca2+ channels in a voltage-independent manner by cytosolic Ba2+ via a screening of Ca2+ from sites that produce either inactivation or a lower probability of opening in the activated state. There would be a closing of these channels at higher [Ba2+] as Ba2+ is forced onto these sites. A refractory period is also required to give repeated pulses of openings.
Ferrier
J
J
Medical Research Council Group in Periodontal Physiology, University of Toronto, Ontario, Canada.
Grygorczyk
C
C
Grygorczyk
R
R
Kesthely
A
A
Lagan
E
E
Xia
S L
SL
D000200:Action Potentials; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D001692:Biological Transport; D008839:Microelectrodes; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D012516:Osteosarcoma; D051381:Rats; D014407:Tumor Cells, Cultured
D001464:Barium