V. Lukyanenko et al., PHARMACOLOGICAL ANALYSIS OF VOLTAGE-DEPENDENT POTASSIUM CURRENTS IN CULTURED SKELETAL MYOCYTES OF THE FROG RANA-TEMPORARIA, General physiology and biophysics, 14(6), 1995, pp. 525-534
Previously, the existence of nine types of outward potassium current (
I-K) was shown. The whole family of I-K may be divided into two groups
: fast transient currents (f) with time to peak less than 70 ms (at te
st potential near 0 mV), and slow (s) components (Lukyanenko et al. 19
93). The latter were completely blocked by 4-aminopyridine (4-AP) and
the former were more sensitive to TEA than slow I-K. In the present st
udy we analyzed the effects of calcium blockers on different types of
I-K using the whole-cell patch-clamp technique. One to seven-day old m
yocytes without slow calcium currents and without contact with nerve c
ells were examined. Extracellullar application of 40-80 mu mol/l dihyd
ropyridine (DHP) antagonist nifedipine did not change maximal conducta
nce of K-channels, but induced a parallel shift by 5-10 mV of chord co
nductance curve along the voltage axis in the direction of more negati
ve potentials. Quinidine in concentrations 30-200 mu mol/l caused a re
versible block of the fast and the slow I-K (C-0.5 = 75 mu mol/l), and
enhanced the current decay (2-3-fold at 150 mu mol/l). Verapamil (VP)
in concentrations 100-700 mu mol/l reduced I-K with dose-dependent ef
fect (C-0.5 = 200 mu mol/l) and changed its kinetic properties. VP 100
mu mol/l caused a complete irreversible block of the slow I-K. VP red
uced the time inactivation constant of fast I-K with a dose-dependent
effect (8-10-fold at 300 mu mol/l), and this effect was stronger durin
g depolarizing pulses. The latter points to the possibility that the f
ast K-channels preferentially bind VP in open state. An analysis of th
e effects suggests that K-channels of the frog myocytes could be divid
ed into 2 groups: 1) K-channels which are irreversibly blocked by VP a
nd 4-AP (slow), and 2) those reversibly inhibited by VP and 4-AP (fast
potassium channels).