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The superficial buffer barrier in venous smooth muscle: sarcoplasmic reticulum refilling and unloading
Author(s) -
Chen Qian,
Breemen Cornelis
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13575.x
Subject(s) - thapsigargin , extracellular , chemistry , biophysics , endoplasmic reticulum , ryanodine receptor , intracellular , egta , atpase , caffeine , calcium , medicine , endocrinology , biochemistry , biology , enzyme , organic chemistry
1 The interaction of Ca 2+ transport in the plasmalemma and the sarcoplasmic reticulum (SR) was investigated in smooth muscle of the rabbit inferior vena cava. We tested the possibility of direct refilling of the SR with extracellular Ca 2+ and of the existence of a vectorial Ca 2+ extrusion pathway from the SR lumen to the extracellular space suggested by earlier results. 2 After depletion with caffeine the SR was loaded with Ca 2+ to increasing levels by incubation in a high potassium 1.5 m m Ca 2+ solution and a 10 m m Ca 2+ zero Na + solution, respectively. Thapsigargin, 2 μ m , (a specific SR Ca 2+ ‐ATPase blocker) completely blocked refilling of the SR in either of the above solutions, indicating that the SR Ca 2+ ‐ATPase is essential for this process. 3 Three different agents, caffeine, ryanodine and thapsigargin, which inhibit Ca 2+ accumulation by the SR, increased the steady state intracellular Ca 2+ concentration in the rabbit inferior vena cava. 4 Measurements of Mn 2+ induced quenching of the intracellular fura‐2 signal during pharmacological manipulation of the SR content showed that these three agents did not stimulate divalent cation entry. 5 On the other hand, stimulation with noradrenaline caused a marked increase in Mn 2+ influx, which was blocked by 2 m m Ni 2+ . Mn 2+ entry stimulated by high K + solution was blocked by 1 μ m diltiazem. 6 We conclude that the SR refilling has to be mediated by the SR Ca 2+ ‐ATPase. Inhibition of Ca 2+ accumulation by the SR causes an increase in the steady state intracellular Ca 2+ concentration. This observation cannot be explained by an increase in Ca 2+ influx into the smooth muscle cells of the rabbit inferior vena cava. Alternatively these results suggest the existence of a continuous vectorial release of Ca 2+ from the SR lumen to the extracellular space.