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LY 97241 accelerates the apparent rate of inactivation of transient outward K+ current: characterization of open channel block.
J Pharmacol Exp Ther. 1995 Jul; 274(1):249-57.JP

Abstract

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)

Authors+Show Affiliations

Lilly Research Laboratory, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7616405

Citation

Zhang, Z H., and M I. Steinberg. "LY 97241 Accelerates the Apparent Rate of Inactivation of Transient Outward K+ Current: Characterization of Open Channel Block." The Journal of Pharmacology and Experimental Therapeutics, vol. 274, no. 1, 1995, pp. 249-57.
Zhang ZH, Steinberg MI. LY 97241 accelerates the apparent rate of inactivation of transient outward K+ current: characterization of open channel block. J Pharmacol Exp Ther. 1995;274(1):249-57.
Zhang, Z. H., & Steinberg, M. I. (1995). LY 97241 accelerates the apparent rate of inactivation of transient outward K+ current: characterization of open channel block. The Journal of Pharmacology and Experimental Therapeutics, 274(1), 249-57.
Zhang ZH, Steinberg MI. LY 97241 Accelerates the Apparent Rate of Inactivation of Transient Outward K+ Current: Characterization of Open Channel Block. J Pharmacol Exp Ther. 1995;274(1):249-57. PubMed PMID: 7616405.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LY 97241 accelerates the apparent rate of inactivation of transient outward K+ current: characterization of open channel block. AU - Zhang,Z H, AU - Steinberg,M I, PY - 1995/7/1/pubmed PY - 1995/7/1/medline PY - 1995/7/1/entrez SP - 249 EP - 57 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 274 IS - 1 N2 - 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) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7616405/LY_97241_accelerates_the_apparent_rate_of_inactivation_of_transient_outward_K+_current:_characterization_of_open_channel_block_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&amp;pmid=7616405 DB - PRIME DP - Unbound Medicine ER -