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Activation of ATP-sensitive outward K+ current by nicorandil (2-nicotinamidoethyl nitrate) in isolated ventricular myocytes.
J Pharmacol Exp Ther. 1989 Jul; 250(1):278-85.JP

Abstract

The vasodilatory agent, nicorandil (2-nicotinamidoethyl nitrate) activates an outward K+ current in cardiac and vascular smooth muscle. This current was studied with the patch clamp technique using isolated guinea pig and rabbit ventricular myocytes. Nicorandil (10(-5) and 10(-4) M) shortened the action potential duration without any significant change in the resting membrane potential. Under voltage clamp, nicorandil increased the time-independent outward current at potentials positive to -80 mV, and decreased the inward current at potentials negative to -90 mV. The drug did not affect Ca++ current activated upon depolarization from the holding potential of -30 mV, or did it influence delayed outward K+ current on repolarization. In rabbit myocytes, nicorandil did not increase the Ca++-sensitive and -insensitive transient outward K+ currents. When the ATP concentration of the pipette solution was reduced from 5 to 2 to 3 mM, nicorandil produced a large increase in outward current, which decreased slightly with time. The increased outward current was antagonized by raising the intracellular ATP concentration. Nicorandil increased the probability of opening of the ATP-sensitive single channel current without affecting its unitary amplitude. These results indicate that nicorandil activates the ATP-sensitive K+ current, which is responsible for shortening of the action potential duration.

Authors+Show Affiliations

Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, Japan.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

2526215

Citation

Hiraoka, M, and Z Fan. "Activation of ATP-sensitive Outward K+ Current By Nicorandil (2-nicotinamidoethyl Nitrate) in Isolated Ventricular Myocytes." The Journal of Pharmacology and Experimental Therapeutics, vol. 250, no. 1, 1989, pp. 278-85.
Hiraoka M, Fan Z. Activation of ATP-sensitive outward K+ current by nicorandil (2-nicotinamidoethyl nitrate) in isolated ventricular myocytes. J Pharmacol Exp Ther. 1989;250(1):278-85.
Hiraoka, M., & Fan, Z. (1989). Activation of ATP-sensitive outward K+ current by nicorandil (2-nicotinamidoethyl nitrate) in isolated ventricular myocytes. The Journal of Pharmacology and Experimental Therapeutics, 250(1), 278-85.
Hiraoka M, Fan Z. Activation of ATP-sensitive Outward K+ Current By Nicorandil (2-nicotinamidoethyl Nitrate) in Isolated Ventricular Myocytes. J Pharmacol Exp Ther. 1989;250(1):278-85. PubMed PMID: 2526215.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of ATP-sensitive outward K+ current by nicorandil (2-nicotinamidoethyl nitrate) in isolated ventricular myocytes. AU - Hiraoka,M, AU - Fan,Z, PY - 1989/7/1/pubmed PY - 1989/7/1/medline PY - 1989/7/1/entrez SP - 278 EP - 85 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 250 IS - 1 N2 - The vasodilatory agent, nicorandil (2-nicotinamidoethyl nitrate) activates an outward K+ current in cardiac and vascular smooth muscle. This current was studied with the patch clamp technique using isolated guinea pig and rabbit ventricular myocytes. Nicorandil (10(-5) and 10(-4) M) shortened the action potential duration without any significant change in the resting membrane potential. Under voltage clamp, nicorandil increased the time-independent outward current at potentials positive to -80 mV, and decreased the inward current at potentials negative to -90 mV. The drug did not affect Ca++ current activated upon depolarization from the holding potential of -30 mV, or did it influence delayed outward K+ current on repolarization. In rabbit myocytes, nicorandil did not increase the Ca++-sensitive and -insensitive transient outward K+ currents. When the ATP concentration of the pipette solution was reduced from 5 to 2 to 3 mM, nicorandil produced a large increase in outward current, which decreased slightly with time. The increased outward current was antagonized by raising the intracellular ATP concentration. Nicorandil increased the probability of opening of the ATP-sensitive single channel current without affecting its unitary amplitude. These results indicate that nicorandil activates the ATP-sensitive K+ current, which is responsible for shortening of the action potential duration. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2526215/Activation_of_ATP_sensitive_outward_K+_current_by_nicorandil__2_nicotinamidoethyl_nitrate__in_isolated_ventricular_myocytes_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2526215 DB - PRIME DP - Unbound Medicine ER -