RT Journal Article SR Electronic T1 LY 97241 accelerates the apparent rate of inactivation of transient outward K+ current: characterization of open channel block. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 249 OP 257 VO 274 IS 1 A1 Z H Zhang A1 M I Steinberg YR 1995 UL http://jpet.aspetjournals.org/content/274/1/249.abstract AB LY 97241 [(LY), p-nitro tertiary amine analog of clofilium] has been shown to prolong action potential duration in vitro but its effects on transient outward potassium current (Ito) are unknown. The authors investigated the effect of LY on Ito in rat ventricular myocytes using whole cell patch clamp techniques. LY resulted in a concentration-dependent inhibition of Ito amplitude (measured 30 msec after onset of depolarization) with an EC50 of 5.85 microM. The inhibitory effect of LY (10 microM) was seen at voltages from -30 to 70 mV (e.g., at 30 mV, LY reduced amplitude from a control of 7.29 +/- 0.30 to 3.05 +/- 0.22 pA/pF, P < .01, n = 10). The voltage-dependent block by LY was fitted by the Boltzmann equation, yielding a voltage for half-maximal block (V1/2) of -25.0 mV with a slope factor (k) of 13.8 mV. LY (10 microM) accelerated the rate of Ito inactivation from 41.9 +/- 3.5 to 16.0 +/- 1.6 msec without an effect on the peak of Ito (n = 10, P < .01). In contrast, 4-aminopyridine (4-AP, 1 mM) had no effect on the rate of inactivation but decreased the peak of Ito from 1.84 +/- 1.6 to 0.71 +/- 0.20 nA (n = 3). The time constant of onset of block (tau B) on Ito by 10 microM LY was fitted to a monoexponential function having a tau B of 14.5 +/- 1.5 msec. LY had no effect on the steady-state inactivation or recovery from inactivation of Ito.(ABSTRACT TRUNCATED AT 250 WORDS)