Store-operated Ca2+ entry modulates sarcoplasmic reticulum Ca2+ loading in neonatal rabbit cardiac ventricular myocytes.
Store-operated Ca2+ entry (SOCE), which is Ca2+ entry triggered by the depletion of intracellular Ca2+ stores, has been observed in many cell types, but only recently has it been suggested to occur in cardiomyocytes. In the present study, we have demonstrated SOCE-dependent sarcoplasmic reticulum (SR) Ca2+ loading (load(SR)) that was not altered by inhibition of L-type Ca2+ channels, reverse mode Na+/Ca2+ exchange (NCX), or nonselective cation channels. In contrast, lowering the extracellular [Ca2+] to 0 mM or adding either 0.5 mM Zn2+ or the putative store-operated channel (SOC) inhibitor SKF-96365 (100 microM) inhibited load(SR) at rest. Interestingly, inhibition of forward mode NCX with 30 microM KB-R7943 stimulated SOCE significantly and resulted in enhanced load(SR). In addition, manipulation of the extracellular and intracellular Na+ concentrations further demonstrated the modulatory role of NCX in SOCE-mediated SR Ca2+ loading. Although there is little knowledge of SOCE in cardiomyocytes, the present results suggest that this mechanism, together with NCX, may play an important role in SR Ca2+ homeostasis. The data reported herein also imply the presence of microdomains unique to the neonatal cardiomyocyte. These findings may be of particular importance during open heart surgery in neonates, in which uncontrolled SOCE could lead to SR Ca2+ overload and arrhythmogenesis.
Huang
Jingbo
J
Cardiac Membrane Research Laboratory, Simon Fraser Univ., 8888 University Dr., Burnaby, BC, Canada V5A 1S6.
van Breemen
Casey
C
Kuo
Kuo-Hsing
KH
Hove-Madsen
Leif
L
Tibbits
Glen F
GF
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D005260:Female; D006352:Heart Ventricles / Q000254:growth & development / Q000378:metabolism*; D017136:Ion Transport; D008297:Male; D046529:Microscopy, Electron, Transmission; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013997:Time Factors
D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium