title: Negative inotropic effect of extracellular calcium buffering in cardiac muscle.
abstract: Heart muscle contracts more vigorously when calcium levels are raised. A transient depletion of calcium from restricted extracellular spaces occurs with each contraction. We decided to maintain the concentration of this ion at a constant level by using an external calcium buffering system. It was found that buffering calcium at a millimolar level (using citrate as a buffer) caused a decrease, rather than an increase in the strength of contraction. The mean reduction in peak tension was by 27% in guinea pig and by 50.5% in frog atrium. This finding is analyzed; its most plausible explanation is the hypothesis that the buffer dissipates a calcium inhomogeneity, consisting of a higher calcium concentration adjacent to the membrane. Alternative interpretations such as intracellular acidosis, were tested experimentally and ruled out.
mesh_terms: D000818:Animals; D001001:Anura; D016275:Atrial Function; D002021:Buffers; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D003864:Depression, Chemical; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*
chemical_list: D002021:Buffers; D002951:Citrates; D019343:Citric Acid; D008274:Magnesium; D002118:Calcium