Osmolality- and Na+ -dependent effects of hyperosmotic NaCl solution on contractile activity and Ca2+ cycling in rat ventricular myocytes.
Hypertonic NaCl solutions have been used for small-volume resuscitation from hypovolemic shock. We sought to identify osmolality- and Na(+)-dependent components of the effects of the hyperosmotic NaCl solution (85 mOsm/kg increment) on contraction and cytosolic Ca(2+) concentration ([Ca(2+)](i)) in isolated rat ventricular myocytes. The biphasic change in contraction and Ca(2+) transient amplitude (decrease followed by recovery) was accompanied by qualitatively similar changes in sarcoplasmic reticulum (SR) Ca(2+) content and fractional release and was mimicked by isosmotic, equimolar increase in extracellular [Na(+)] ([Na(+)](o)). Raising osmolality with sucrose, however, augmented systolic [Ca(2+)](i) monotonically without change in SR parameters and markedly decreased contraction amplitude and diastolic cell length. Functional SR inhibition with thapsigargin abolished hyperosmolality effects on [Ca(2+)](i). After 15-min perfusion, both hyperosmotic solutions slowed mechanical relaxation during twitches and [Ca(2+)](i) decline during caffeine-evoked transients, raised diastolic and systolic [Ca(2+)](i), and depressed systolic contractile activity. These effects were greater with sucrose solution, and were not observed after isosmotic [Na(+)](o) increase. We conclude that under the present experimental conditions, transmembrane Na(+) redistribution apparently plays an important role in determining changes in SR Ca(2+) mobilization, which markedly affect contractile response to hyperosmotic NaCl solutions and attenuate the osmotically induced depression of contractile activity.
Departamento de Engenharia Biomédica/Faculdade de Engenharia Elétrica e de Computação, Universidade Estadual de Campinas, Campinas, SP, Brazil.
Rafael A
RA
Ricardo
Rosana A
RA
Bassani
José W M
JW
Bassani
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D012964:Sodium / Q000378:metabolism*; D013395:Sucrose / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D012462:Saline Solution, Hypertonic; D002110:Caffeine; D013395:Sucrose; D019284:Thapsigargin; D012964:Sodium; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium