Effects of IVA on the action potentials of LAMs
IVA (0.3 μM) reduced the AP amplitude (APA) and maximum upstroke
velocity of the AP (Vmax) from 139.02 ± 5.43 mV and
187.47 ± 14.85 V/s to 128.03 ± 5.37 mV and 175.12 ± 14.73 V/s,p<0.05 vs. baseline, Table 2), shortened
APD30 from 131.06 ± 4.17 to 111.00 ± 9.92 V/s (n=12,p<0.05 )
without changing resting membrane potential (RMP). IVA (10 µM) reduced
RMP (-72.45 ± 3.81 mV) and shortened the APD50 and
APD90 (n=12, p<0.05 ).
ATX-II (1 nM) slowed Vmax, and prolonged
APD30, APD50 and APD90(n = 8 cells/4 rabbits, p <0.05 vs. 0 µM IVA, Table 3
and Fig 3A) without changing RMP and APA. In the presence of ATX-II,
administration of IVA (0.3 and 3 μM) shortened the
APD30, APD50 and APD90values from 159.67 ± 13.07, 179.97 ± 20.69 and 260.94 ± 19.26 ms to
91.13 ± 23.85, 122.71 ± 25.47 and 190.71 ± 29.52 ms(p<0.05 vs. ATX-II alone), respectively. However,
administration of ACh alone increased the myocytes’ RMP from -78.83 ±
1.81 to -65.72 ± 3.61 mV, decreased the APA from 141.36 ± 1.98 mV to
123.78 ± 4.13 mV (n = 8, p<0.05 vs. baseline, Table 3),
and shortened the values of APD30, APD50and APD90 from 130.71 ± 17.68, 153.83 ± 15.49, and
220.34 ± 14.82 ms to 91.99±17.60, 142.04±17.85, and 146.47±8.89 ms at
most, respectively (n = 8s, p<0.05 vs. baseline, Table
3) of LAMs. In the continued presence of ACh, IVA (0.3 and 3 μM)
maximally prolonged the ACh-induced shortening of APD30,
APD50 and APD90 to 101.49 ± 17.61,
131.85 ± 13.47 and 140.18 ± 5.15 ms, respectively
(p<0.05 vs. ACh alone).
The
present results indicate that IVA affects the depolarization of APs in
atrial cells while influencing the whole AP process in ATX-II- and
ACh-pretreated cells.