Tetraphenylboron causes Ca²⁺ release in isolated sarcopladmic reticulum and in skinned muscle fibers

The lipophilic anion tetraphenylboron (TPB^-) but not the lipophilic cation tetraphenylarsonium (TPA⁺) inhibited ATP-dependent Ca²⁺ accumulation by isolated sarcoplasmic reticulum. TPB^- did not inhibit ATP hydrolysis but did induce Ca²⁺ release from preloaded vesicles. It did not appear to disrupt lipid bilayers or to act as a Ca²⁺ ionophore since it had no effect on the Ca²⁺ content of phospholipid vesicles. TPB^- also induced Ca²⁺ release from sarcoplasmic reticulum in chemically skinned muscle fibers causing tension development. In contrast to other Ca²⁺-releasing agents such as caffeine, proton ionophores, or quercetin, the rise to peak tension was slow and tension was sustained, suggesting that Ca²⁺ release channels, once opened by TPB^-, were held open as long as the compound was present in the membrane. Ca²⁺ uptake was re-established upon removal of TPB^- or addition of TPA⁺. TPB^- or TPA⁺ would probably distribute within the membrane, altering surface charges on both sides of the membrane. The fact that only a negatively charged ion brought about opening of Ca²⁺ release channels suggests that specific surface charges control Ca²⁺ release channels in sarcoplasmic reticulum. Although we have not been able to prove that TPB^- acts exclusively on physiologically relevant Ca²⁺ release channels, we have shown that TPB^- does not release Ca²⁺ from proteoliposomes reconstituted with the Ca²⁺ + Mg²⁺ ATPase. Thus TPB^- does not induce Ca²⁺ release through channels formed by the ATPase molecule.