Abstract
Positive feedback of Calcium (Ca)-induced Ca release is the mechanism of Ca spark formation in cardiac myocytes. To initiate this process, a certain amount of Ca in the cleft space is necessary. When the membrane potential becomes higher during excitation-contraction coupling, Ca can enter through both Ca current (I CaL) and sodium-calcium exchanger (NCX) and may activate ryanodine receptors to initiate a Ca spark. On the other hand, at the resting membrane potential (V m ∼-80 mV), NCX removes Ca from the cell (forward mode). If Ca released from the sarcoplasmic reticulum is quickly removed via forward mode NCX before Ca-induced Ca release starts, the Ca release becomes nonspark Ca leak. This would also be influenced by the cleft/noncleft distribution of NCX, which is unknown. Using a physiologically detailed mathematical model of subcellular Ca cycling, we analyze how NCX strength and distribution alter Ca spark formation. During excitation-contraction coupling, most Ca sparks are induced by I CaL with very few due to NCX current. At the resting membrane potential if most NCX is localized to the cleft, spontaneous Ca sparks are significantly reduced.
| Original language | English |
|---|---|
| Pages (from-to) | L31-L33 |
| Journal | Biophysical Journal |
| Volume | 102 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 18 2012 |
Bibliographical note
Funding Information:This work was supported by a postdoctoral fellowship from the American Heart Association, Western States Affiliate (D.S.), National Institutes of Health grant HL109501 (S.D.), and National Institutes of Health grant R37-HL30077 (D.M.B.).
ASJC Scopus subject areas
- Biophysics