ryanodine and tetramethrin

The aim was to describe a novel form of non-neurogenic coronary artery contraction.. Superfused cattle coronary artery preparations in vitro were placed between platinum electrodes and stimulated.. The preparations responded to exceedingly brief transmural stimulation (a single ten thousandth of a second pulse) with long lasting [150(SEM 18.5) s] contractions. These previously undescribed contractions were not reduced by neural blockade nor did they involve free radicals, prostaglandins, or the endothelium. In contrast to the rapid loss of responses to KCl in zero calcium Krebs solution, responses to stimulation were only progressively diminished over many minutes, suggesting involvement of internal calcium stores. The L channel calcium antagonists nifedipine and diltiazem markedly reduced contractions to KCl but did not materially alter those to 1, 5, or 10 stimulation pulses, nor did the T channel antagonist tetramethrin, further supporting the involvement of stored calcium in contractions to stimulation. Evidence was obtained that neither Na+/K(+)-ATPase nor the Na+/Ca+ exchanger are involved in the contractions to stimulation. Ryanodine in zero calcium Krebs solution potentiated contractions to stimulation with 10 pulses and also to endothelin, but depressed contractions to U 46619.. Stimulation at excitation parameters well below those associated with neurotransmitter release activates a highly effective contraction sequence that may use a ryanodine insensitive pool of bound calcium. This novel process may have physiological and pathophysiological relevance and provides a means of activating contraction in a coronary artery and studying its time course and contributory components, without the complicating participation of an agonist drug.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Calcium; Cattle; Coronary Vessels; Diltiazem; Electric Stimulation; In Vitro Techniques; Insecticides; Muscle Contraction; Muscle, Smooth, Vascular; Nifedipine; Prostaglandin Endoperoxides, Synthetic; Pyrethrins; Ryanodine; Thromboxane A2; Vasoconstrictor Agents

The effect of insulin-like growth factor I (IGF-I) on cytoplasmic free calcium concentration ([Ca2+]c) was studied in single BALB/c 3T3 cells by monitoring fura-2 fluorescence. In primed competent cells, IGF-I (1 nM) increased [Ca2+]c in approximately 60% of the cells tested. IGF-I-mediated elevation of [Ca2+]c was observed after a 4- to 17-min lag period. Elevation of [Ca2+]c was only transient but was followed by repetitive increases in [Ca2+]c. The interval between each peak was quite constant in each cell at a given concentration of IGF-I. When the concentration of IGF-I was reduced, both the latent period and interval of each peak were prolonged, whereas amplitude of the increase in [Ca2+]c was not altered. In medium containing 10 microM extracellular calcium, IGF-I did not cause any increase in [Ca2+]c. Likewise, blockade of IGF-induced calcium entry by either cobalt or tetramethrin abolished IGF-I action on [Ca2+]c. IGF-I-mediated oscillation was not affected by either ryanodine or caffeine, compounds that affect calcium-induced calcium release. In addition, pretreatment of the cell with neomycin did not affect IGF-I-mediated oscillation. In agreement with this, IGF-I did not augment production of [3H]inositol trisphosphate in cells prelabeled with [3H]inositol. These results indicate that IGF-I induces oscillation of [Ca2+]c in a single primed competent cell and that the oscillation is totally dependent on IGF-I-mediated calcium entry.

Topics: 3T3 Cells; Animals; Caffeine; Calcium; Cobalt; Cytoplasm; Fura-2; Inositol; Inositol Phosphates; Insulin-Like Growth Factor I; Kinetics; Mice; Oscillometry; Pyrethrins; Ryanodine; Spectrometry, Fluorescence