Thimerosal enhances agonist-specific differences between [Ca2+]i oscillations induced by phenylephrine and ATP in single rat hepatocytes.
Single rat hepatocytes, microinjected with the Ca(2+)-sensitive photoprotein aequorin, respond to agonists acting through the phosphoinositide signalling pathway by the generation of oscillations in cytosolic free Ca2+ concentration ([Ca2+]i). The duration of [Ca2+]i transients generated is characteristic of the stimulating agonist; the differences lie in the rate of fall of [Ca2+]i from its peak. We considered that differential sensitivity of the InsP3 receptor may underlie agonist specificity. The thiol reagent, thimerosal, is known to increase the sensitivity of the Ca2+ stores to InsP3 by increasing the affinity of the InsP3 receptor for InsP3 in rat hepatocytes. We show here that a low dose of thimerosal (1 microM), insufficient alone to elevate [Ca2+]i, potentiates [Ca2+]i oscillations induced by phenylephrine or ATP in single, aequorin-injected, rat hepatocytes. Moreover, thimerosal enhances both the frequency and amplitude of phenylephrine-induced oscillations, whereas, in contrast, ATP-induced oscillations undergo an increase in the duration of the falling phase of individual [Ca2+]i transients. Thimerosal, therefore, enhances, rather than eliminates, agonist-specific differences in the hepatocyte [Ca2+]i oscillator.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000331:Aequorin / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks; D002118:Calcium / Q000819:agonists* / Q000378:metabolism*; D002478:Cells, Cultured; D008099:Liver / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013849:Thimerosal / Q000494:pharmacology*