Ba²⁺-induced action potentials in osteoblastic cells

Summary

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°C following the addition of 10 or 20mm 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°C in the presence of from 10 to 110mm Ba²⁺ in the bathing medium. The current pulses were not seen at 22°C in the presence of 110mm 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.