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| Title: | EXTRACELLULAR POTASSIUM DEPENDENT NEGATIVE DROMOTROPIC ACTIONS OF NICORANDIL: EXPERIMENTAL AND COMPUTATIONAL STUDY | |
| DOI No: | 10.1142/9789812702234_0020 | |
| Source: | ADVANCES IN ELECTROCARDIOLOGY 2004 (pp 82-86) | |
| Author(s): | TORU MARUYAMA
This work was partly supported by a Research Grant for Advanced Medical Science and Treatment from the Ministry of Posts and Telecommunications of Japan. Institute of Health Science, Kyushu University, Kasuga 816-8580, Japan FUMIAKI KUMA Institute of Health Science, Kyushu University, Kasuga 816-8580, Japan Department of Medicine, Kyushu University, Fukuoka, 812-8582, Japan HIROYUKI ITO Institute of Health Science, Kyushu University, Kasuga 816-8580, Japan Department of Medicine, Kyushu University, Fukuoka, 812-8582, Japan YOSHIKAZU KAJI Institute of Health Science, Kyushu University, Kasuga 816-8580, Japan Department of Medicine, Kyushu University, Fukuoka, 812-8582, Japan TATSUTO KIYOSUE Department of Nutritional Sciences, Faculty of Health and Welfare, Seinan Jo Gakuin University, Kitakyushu, 803-0835, Japan |
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| Abstract: | Dromotropic effect of nicorandil, a KATP channel opener, was investigated by guinea pig papillary muscle under the recordings of extracellular and action potentials during conduction. The correlation of myocardial internal longitudinal resistance (ri) assumed to reflect global gap junctional resistance, maximum rate of rise of the action potential upstroke (Vmax), and conduction velocity was examined under the various external potassium concentrations ([K+]e; 3.0 to 12.0 mM) and application of 100 uM nicorandil. At 3.0mM [K+]e, nicorandil caused significant (p < 0.05) hyperpolarization of the resting membrane potential, but reduced the Vmax. Concomitantly, conduction was slightly but significantly slowed by nicorandil (p < 0.05) at low (3.0 mM) [K+]e. Nicorandil did not have these effects at physiologic (5.4 mM) and elevated (9.0 to 12.0 mM) [K+]e. A computer simulation of single ventricular cell model predicted a delay in action potential take-off and a decrease in Vmax after acceleration of KATP channel opening. In conclusion, nicorandil exerts negative dromotropism in spite of membrane hyperpolarization at low [K+]e, which has clinical implication in such circumstances. | |
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