title: Pharmacological analysis of voltage-dependent potassium currents in cultured skeletal myocytes of the frog Rana temporaria.
abstract: Previously, the existence of nine types of outward potassium current (IK) was shown. The whole family of IK may be divided into two groups: fast transient currents (f) with time to peak less than 70 ms (at test potential near 0 mV), and slow (s) components (Lukyanenko et al. 1993). The latter were completely blocked by 4-aminopyridine (4-AP) and the former were more sensitive to TEA than slow IK. In the present study we analyzed the effects of calcium blockers on different types of IK using the whole-cell patch-clamp technique. One to seven-day-old myocytes without slow calcium current and without contact with nerve cells were examined. Extracellullar application of 40-80 mumol/l dihydropyridine (DHP) antagonist nifedipine did not change maximal conductance of K-channels, but induced a parallel shift by 5-10 mV of chord conductance curve along the voltage axis in the direction of more negative potentials. Quinidine in concentrations 30-200 mumol/l caused a reversible block of the fast and the slow IK (C0.5 = 75 mumol/l), and enhanced the current decay (2-3-fold at 150 mumol/l). Verapamil (VP) in concentrations 100-700 mumol/l reduced IK with dose-dependent effect (C0.5 = 200 mumol/l) and changed its kinetic properties. VP 100 mumol/l caused a complete irreversible block of the slow IK. VP reduced the time inactivation constant of fast IK with a dose-dependent effect (8-10-fold at 300 mumol/l), and this effect was stronger during depolarizing pulses. The latter points to the possibility that the fast K-channels preferentially bind VP in open state. An analysis of the effects suggests that K-channels of the frog myocytes could be divided into 2 groups: 1) K-channels which irreversibly blocked by VP and 4-AP (slow), and 2) those reversibly inhibited by VP and 4-AP (fast potassium channels).
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: V
authors.initials: V
authors.lastname: Lukyanenko
authors.forename: I E
authors.initials: IE
authors.lastname: Katina
authors.forename: G A
authors.initials: GA
authors.lastname: Nasledov
authors.forename: D A
authors.initials: DA
authors.lastname: Terentyev
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004625:Embryo, Nonmammalian; D008564:Membrane Potentials / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011802:Quinidine / Q000494:pharmacology; D011896:Rana temporaria; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D015221:Potassium Channels; C038806:1,4-dihydropyridine; D015761:4-Aminopyridine; D014700:Verapamil; D009543:Nifedipine; D011802:Quinidine