Diastolic calcium release controls the beating rate of rabbit sinoatrial node cells: numerical modeling of the coupling process.
Recent studies employing Ca2+ indicators and confocal microscopy demonstrate substantial local Ca2+ release beneath the cell plasma membrane (subspace) of sinoatrial node cells (SANCs) occurring during diastolic depolarization. Pharmacological and biophysical experiments have suggested that the released Ca2+ interacts with the plasma membrane via the ion current (INaCa) produced by the Na+/Ca2+ exchanger and constitutes an important determinant of the pacemaker rate. This study provides a numerical validation of the functional importance of diastolic Ca2+ release for rate control. The subspace Ca2+ signals in rabbit SANCs were measured by laser confocal microscopy, averaged, and calibrated. The time course of the subspace [Ca2+] displayed both diastolic and systolic components. The diastolic component was mainly due to the local Ca2+ releases; it was numerically approximated and incorporated into a SANC cellular electrophysiology model. The model predicts that the diastolic Ca2+ release strongly interacts with plasma membrane via INaCa and thus controls the phase of the action potential upstroke and ultimately the final action potential rate.
Maltsev
Victor A
VA
Gerontology Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224-6825, USA.
Vinogradova
Tatiana M
TM
Bogdanov
Konstantin Y
KY
Lakatta
Edward G
EG
Stern
Michael D
MD
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003198:Computer Simulation; D008564:Membrane Potentials / Q000502:physiology; D018613:Microscopy, Confocal; D009119:Muscle Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D012849:Sinoatrial Node / Q000378:metabolism* / Q000502:physiology
D002118:Calcium