E-4031 enhanced Ca2+ transient and ventricular myocytes contraction via reverse mode Na+/Ca2+ exchange in normal and hypertrophic rats.

AIM: To study the effects of
N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl]carbonyl]phenyl]methanesul
fonamide dihydrochloride dihydrate (E-4031), a specific Ik blocker, on Ca2+
transient and cell contraction of normal and hypertrophied rat ventricular
myocytes.
METHODS: Electrically triggered Ca2+ transient and cell shortening were measured
simultaneously using the Ion Imaging System with charge coupled digital (CCD)
camera.
RESULTS: E-4031 (10 micromol/L) increased Ca2+ transient and cell shortening from
(210+/-49) and (3.0+/-0.8) micron to (245+/-47) and (3.6+/-1.0) micron,
respectively (P<0.05) in normal cardiomyocytes and from (196+/-54) and
(3.0+/-1.3) micron to (240+/-49) and (3.6+/-1.3) micron respectively (P<0.05) in
hypertrophied cardiomyocytes, while did not change calcium sensitivity in both
groups. KB-R7943 completely blocked the activating effects induced by E-4031 in
both of normal and hypertrophied cardiomyocytes. Nicardipine did not block the
increasing effects of E-4031.
CONCLUSION: E-4031 increased Ca2+ transient and cell contraction via stimulating
reverse mode of Na+/Ca2+ exchange while without influencing calcium sensitivity.
These effects were more notable in hypertrophied cardiomyocytes than in normal
myocytes.