Effect of Ca2+ agonists in the perfused liver: Determination via laser scanning confocal microscopy

Kentaro Motoyama, Irene E. Karl, M. Wayne Flye, Dale F. Osborne, Richard S. Hotchkiss

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Ca2+ is a critical intracellular second messenger, but few studies have examined Ca2+ signaling in whole organs. The amplitude and frequency of Ca2+ oscillations encode important cellular information. Using laser scanning confocal microscopy in the indo 1 acetoxymethyl ester dye-loaded rat liver, we investigated the effect of various Ca2+ agonists that act at distinct mechanistic sites on Ca2+ signaling. Perfusion with supra- threshold doses of arginine vasopressin (AVP) (2-20 nM) caused a single Ca2+ wave that originated in the pericentral vein region and spread centrifugally to the periportal area. Lower doses of AVP (0.2-2 nM) caused multiple Ca2+ waves and Ca2+ oscillations. Perfusion with ATP (1.4-17.5 μM) caused rapid transient elevations in intracellular free Ca2+ concentration ([Ca2+](i)) occurring in isolated hepatocytes or groups of hepatocytes throughout the lobule and were of shorter duration than those due to AVP. Also in contrast to AVP, there was no specific anatomic location within the hepatic lobule that was more susceptible to ATP. Thapsigargin and cyclopiazonic acid did not cause a Ca2+ wave but rather produced a uniform and fairly simultaneous increase in [Ca2+](i) in all hepatocytes in the lobule. Perfusion with 14 μM ryanodine produced a single transient spike in [Ca2+](i) in a small number (<2%) of hepatocytes. Dantrolene, an inhibitor of Ca2+ release, reduced the increased [Ca2+](i) occurring after AVP. Insight into the mechanism of action of these Ca2+-active compounds on Ca2+ signaling in the intact liver is provided.

Original languageEnglish
Pages (from-to)R575-R585
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume276
Issue number2 45-2
DOIs
StatePublished - Feb 1999

Keywords

  • Dantrolene
  • Hepatocytes
  • Ryanodine
  • Thapsigargin
  • Vasopressin

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