%0 Journal Article %1 Webe_2003_950 %A Weber, Christopher R %A Ginsburg, Kenneth S %A Bers, Donald M %D 2003 %J Circ. Res. %K 12702644 Action Allosteric Animals, Calcium, Cardiac, Cell Cells, Conductivity, Congestive, Contraction, Cultured, Electric Electrophysiology, Exchanger, Failure, Gov't, Heart Humans, Ion Ions, Kinetics, Membrane, Myocardial Myocytes, Non-U.S. P.H.S., Patch-Clamp Potentials, Rabbits, Regulation, Research Separation, Sodium, Sodium-Calcium Support, Techniques, Transport, U.S. %N 9 %P 950--952 %R 8.7F %T Cardiac submembrane Na$^+$ transients sensed by Na$^+$-Ca$^2+$ exchange current. %U http://dx.doi.org/8.7F %V 92 %X Na$^+$ influx via INa during cardiac action potentials can raise bulk Na$^+$i by 10 to 15 micromol/L. However, larger rises in submembrane Na$^+$ (Na$^+$sm) local to Na$^+$-Ca$^2+$ exchangers (NCX) could enhance Ca$^2+$ influx via NCX (and Ca$^2+$-induced Ca$^2+$ release). We tested whether INa could increase Na$^+$sm, using NCX current (INCX) as a biosensor in rabbit ventricular myocytes (with Ca$^2+$i buffered, Na$^+$i=10 mmol/L, and other currents blocked). We measured INCX as early as 5 ms after INa. Prior INa activation did not affect INCX at physiological membrane potentials (Em=-100 to +50 mV), but for Em >+50 mV (where INCX is especially sensitive to Na$^+$i), INCX shifted outward. At 5 ms and +100 mV, INa shifted INCX outward by 0.23 A/F (corresponding to DeltaNa$^+$sm=0.24 mmol/L). The effect of INa dissipated with a time constant of approximately 15 ms. Thus, the impact of INa on NCX is almost undetectable at physiological Em and short lived. This suggests that INa effects on excitation-contraction coupling (via outward INCX) are minimal and limited to early during the action potential. However, local DeltaNa$^+$sm during INa may be 60 times higher than bulk DeltaNa$^+$i.

@article{Webe_2003_950, abstract = {{N}a$^{+}$ influx via INa during cardiac action potentials can raise bulk [{N}a$^{+}$]i by 10 to 15 micromol/L. However, larger rises in submembrane [{N}a$^{+}$] ([{N}a$^{+}$]sm) local to {N}a$^{+}$-{C}a$^{2+}$ exchangers (NCX) could enhance {C}a$^{2+}$ influx via NCX (and {C}a$^{2+}$-induced {C}a$^{2+}$ release). We tested whether INa could increase [{N}a$^{+}$]sm, using NCX current (INCX) as a biosensor in rabbit ventricular myocytes (with [{C}a$^{2+}$]i buffered, [{N}a$^{+}$]i=10 mmol/L, and other currents blocked). We measured INCX as early as 5 ms after INa. Prior INa activation did not affect INCX at physiological membrane potentials (Em=-100 to +50 mV), but for Em >+50 mV (where INCX is especially sensitive to [{N}a$^{+}$]i), INCX shifted outward. At 5 ms and +100 mV, INa shifted INCX outward by 0.23 A/F (corresponding to Delta[{N}a$^{+}$]sm=0.24 mmol/L). The effect of INa dissipated with a time constant of approximately 15 ms. Thus, the impact of INa on NCX is almost undetectable at physiological Em and short lived. This suggests that INa effects on excitation-contraction coupling (via outward INCX) are minimal and limited to early during the action potential. However, local Delta[{N}a$^{+}$]sm during INa may be 60 times higher than bulk Delta[{N}a$^{+}$]i.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Weber, Christopher R and Ginsburg, Kenneth S and Bers, Donald M}, biburl = {https://www.bibsonomy.org/bibtex/260b9e278d005f7f4b1db3cf8222b99d5/hake}, description = {The whole bibliography file I use.}, doi = {8.7F}, file = {Webe_2003_950.pdf:Webe_2003_950.pdf:PDF}, interhash = {5a043c56eac637dc7915105858031f00}, intrahash = {60b9e278d005f7f4b1db3cf8222b99d5}, journal = {Circ. Res.}, key = 149, keywords = {12702644 Action Allosteric Animals, Calcium, Cardiac, Cell Cells, Conductivity, Congestive, Contraction, Cultured, Electric Electrophysiology, Exchanger, Failure, Gov't, Heart Humans, Ion Ions, Kinetics, Membrane, Myocardial Myocytes, Non-U.S. P.H.S., Patch-Clamp Potentials, Rabbits, Regulation, Research Separation, Sodium, Sodium-Calcium Support, Techniques, Transport, U.S.}, month = May, number = 9, pages = {950--952}, pii = {01.RES.0000071747.61468.7F}, pmid = {12702644}, timestamp = {2009-06-03T11:21:36.000+0200}, title = {Cardiac submembrane [{N}a$^{+}$] transients sensed by {N}a$^{+}$-{C}a$^{2+}$ exchange current.}, url = {http://dx.doi.org/8.7F}, volume = 92, year = 2003 }