Abstract
Na+ influx via INa during cardiac action potentials can raise bulk [Na+]i by 10 to 15 μmol/L. However, larger rises in submembrane [Na+] ([Na+]sm) local to Na+-Ca2+ exchangers (NCX) could enhance Ca2+ influx via NCX (and Ca2+-induced Ca2+ release). We tested whether INa could increase [Na+]sm, using NCX current (INCX) as a biosensor in rabbit ventricular myocytes (with [Ca2+]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 Δ[Na+]sm=0.24 mmol/L). The effect of INa dissipated with a time constant of ≈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 Δ[Na+]sm during INa may be 60 times higher than bulk Δ[Na+]i.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 950-952 |
| Number of pages | 3 |
| Journal | Circulation Research |
| Volume | 92 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 16 2003 |
| Externally published | Yes |
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Keywords
- Excitation-contraction coupling
- Na current
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Cardiac submembrane [Na+] transients sensed by Na+-Ca2+ exchange current. / Weber, Christopher R.; Ginsburg, Kenneth S; Bers, Donald M.
In: Circulation Research, Vol. 92, No. 9, 16.05.2003, p. 950-952.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cardiac submembrane [Na+] transients sensed by Na+-Ca2+ exchange current
AU - Weber, Christopher R.
AU - Ginsburg, Kenneth S
AU - Bers, Donald M
PY - 2003/5/16
Y1 - 2003/5/16
N2 - Na+ influx via INa during cardiac action potentials can raise bulk [Na+]i by 10 to 15 μmol/L. However, larger rises in submembrane [Na+] ([Na+]sm) local to Na+-Ca2+ exchangers (NCX) could enhance Ca2+ influx via NCX (and Ca2+-induced Ca2+ release). We tested whether INa could increase [Na+]sm, using NCX current (INCX) as a biosensor in rabbit ventricular myocytes (with [Ca2+]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 Δ[Na+]sm=0.24 mmol/L). The effect of INa dissipated with a time constant of ≈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 Δ[Na+]sm during INa may be 60 times higher than bulk Δ[Na+]i.
AB - Na+ influx via INa during cardiac action potentials can raise bulk [Na+]i by 10 to 15 μmol/L. However, larger rises in submembrane [Na+] ([Na+]sm) local to Na+-Ca2+ exchangers (NCX) could enhance Ca2+ influx via NCX (and Ca2+-induced Ca2+ release). We tested whether INa could increase [Na+]sm, using NCX current (INCX) as a biosensor in rabbit ventricular myocytes (with [Ca2+]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 Δ[Na+]sm=0.24 mmol/L). The effect of INa dissipated with a time constant of ≈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 Δ[Na+]sm during INa may be 60 times higher than bulk Δ[Na+]i.
KW - Excitation-contraction coupling
KW - Na current
UR - http://www.scopus.com/inward/record.url?scp=0037688015&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037688015&partnerID=8YFLogxK
U2 - 10.1161/01.RES.0000071747.61468.7F
DO - 10.1161/01.RES.0000071747.61468.7F
M3 - Article
C2 - 12702644
AN - SCOPUS:0037688015
VL - 92
SP - 950
EP - 952
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 9
ER -