Effects of antisense oligonucleotides to the cardiac Na+/Ca2+ exchanger on cultured cardiac myocytes.
Antisense oligodeoxynucleotides based on the sequence of the cardiac Na+/Ca2+ exchanger were used to study the effects of decreasing expression of this protein on Na(+)-dependent Ca2+ uptake activity and on the spontaneous beating rate of cultured rat cardiac myocytes. Antisense oligos reduced Na+/Ca2+ exchanger activity of myocytes approximately 30-40%, compared to sense-treated or untreated controls. Antisense treatment also increased the spontaneous beating rate of myocardial cells from an average rate of 40 beats to 69 beats per minute, compared to sense-treated or untreated controls. These results indicate that reduced expression of the Na+/Ca2+ exchanger significantly alters intracellular Ca2+ regulation leading to an enhanced spontaneous beating rate and, presumably, a shortened duration of the cardiac cycle in developing myocytes.
Takahashi
K
K
Faculty of Pharmaceutical Science, Osaka University, Japan.
Bland
K S
KS
Islam
S
S
Michaelis
M L
ML
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D016376:Oligonucleotides, Antisense; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium