Effects of neuraminidase on cellular calcium and contraction in cultured cardiac myocytes.
Mammalian plasma membranes, including the myocardial sarcolemma, are abundantly glycosylated. Sialic acid is a ubiquitous anionic sugar found at the periphery of sarcolemmal glycoconjugates. The physiological role of this sugar is not clear, but neuraminidase, which specifically hydrolyzes sialic acid from the sarcolemma, has been found to increase calcium exchange, cause electrophysiological abnormalities, and enhance the transient (T) calcium current in cardiac myocytes. The purpose of this study was to better characterize the effect of neuraminidase on cellular calcium (Ca) and contractile function. Neuraminidase removed up to 57% of total sialic acid from the cells. 45Ca exchange was measured and neuraminidase was found to increase cell calcium proportional to the amount of sialic acid removed (18.6 +/- 0.8 mmol/kg dry w, maximally). Over 80% of the increment in calcium remained rapidly exchangeable (t1/2 less than 15 s) under non-perfusion limited conditions and was inhibited by cations (La greater than Cd greater than Mn greater than Mg) and nifedipine. Using a video-monitoring system, neuraminidase was observed to transiently increase cell shortening during contraction (30 +/- 9%), with progression to arrhythmias followed by cessation of contraction. These results indicate that neuraminidase, probably by removing sarcolemmal sialic acid residues, greatly augments cellular calcium in cultured cardiac myocytes. Most of the increment in Ca induced by neuraminidase was very rapidly exchangeable and most likely mediated by a Ca specific mechanism. Additionally, neuraminidase treatment altered contractile function in a manner consistent with elevated cellular Ca. Despite the many-fold increase in cellular Ca induced by sialic acid removal, cells recovered and demonstrated rhythmic contractions upon return to control incubation conditions.
Yee
H F
HF
Department of Medicine, University of California, Los Angeles School of Medicine 90024.
Kuwata
J H
JH
Langer
G A
GA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012794:Sialic Acids / Q000378:metabolism
D012794:Sialic Acids; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D011188:Potassium; D002118:Calcium