Citrate decreases Ca current and changes selectivity of cardiac Ca channels

Previous studies using citrate as a low affinity Ca buffer have shown that this agent inhibits myocardial contractions and neurotransmitter release. Using several different low affinity Ca buffers we have demonstrated that these effects are unlikely to be attributable to Ca buffering per se. Here we demonstrate that citrate can directly inhibit Ca current (ICa). The decrease in ICa appears to be due to shifts in channel gating (due to surface charge effects) and also to a decrease in channel selectivity for Ca over monovalent ions.