Abstract
1. Effects of okadaic acid on electrical responses and spontaneous activity in the dominant pacemaker cells of rabbit sinus node were investigated by use of microelectrode techniques. 2. Okadaic acid (10(-5) M to 4 x 10(-5) M) caused a shortening of cycle length of spontaneous firing (SPCL) accompanied by increases in both maximum upstroke velocity at phase 0 (Vmax) and amplitude of action potential. 3. All of the effects of okadaic acid were relatively well preserved in a low-Ca2+ medium (0.12 mM). Okadaic acid restored the spontaneous activity of sinus node pacemaker cells even in a Ca2(+)-deficient medium. 4. The effects of okadaic acid were markedly inhibited or abolished in a low Na+ medium (24 mM or 70 mM) and in the presence of a slow channel blocking agent, verapamil (10(-6) M). 5. In voltage-clamp experiments using a two-microelectrode technique, okadaic acid (10(-5) M) caused an increase in the slow inward current without affecting the outward current. At a higher concentration (4 x 10(-5) M), the drug increased the outward current. 6. These results indicate that okadaic acid causes an increase in spontaneous activity of sinus node pacemaker cells mediated by an enhancement of slow inward current (Isi) through verapamil-sensitive Ca2+ channels.
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- Bialojan C., Rüegg J. C., Takai A. Effects of okadaic acid on isometric tension and myosin phosphorylation of chemically skinned guinea-pig taenia coli. J Physiol. 1988 Apr;398:81–95. doi: 10.1113/jphysiol.1988.sp017030. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bleeker W. K., Mackaay A. J., Masson-Pévet M., Bouman L. N., Becker A. E. Functional and morphological organization of the rabbit sinus node. Circ Res. 1980 Jan;46(1):11–22. doi: 10.1161/01.res.46.1.11. [DOI] [PubMed] [Google Scholar]
- Bonke F. I. Electronic spread in the sinoatrial node of the rabbit heart. Pflugers Arch. 1973 Mar 5;339(1):17–23. doi: 10.1007/BF00586978. [DOI] [PubMed] [Google Scholar]
- Brum G., Osterrieder W., Trautwein W. Beta-adrenergic increase in the calcium conductance of cardiac myocytes studied with the patch clamp. Pflugers Arch. 1984 Jun;401(2):111–118. doi: 10.1007/BF00583870. [DOI] [PubMed] [Google Scholar]
- Campbell D. L., Giles W. R., Hume J. R., Noble D., Shibata E. F. Reversal potential of the calcium current in bull-frog atrial myocytes. J Physiol. 1988 Sep;403:267–286. doi: 10.1113/jphysiol.1988.sp017249. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erdödi F., Rokolya A., Di Salvo J., Bárány M., Bárány K. Effect of okadaic acid on phosphorylation-dephosphorylation of myosin light chain in aortic smooth muscle homogenate. Biochem Biophys Res Commun. 1988 May 31;153(1):156–161. doi: 10.1016/s0006-291x(88)81202-6. [DOI] [PubMed] [Google Scholar]
- Hescheler J., Mieskes G., Rüegg J. C., Takai A., Trautwein W. Effects of a protein phosphatase inhibitor, okadaic acid, on membrane currents of isolated guinea-pig cardiac myocytes. Pflugers Arch. 1988 Aug;412(3):248–252. doi: 10.1007/BF00582504. [DOI] [PubMed] [Google Scholar]
- Irisawa H. Comparative physiology of the cardiac pacemaker mechanism. Physiol Rev. 1978 Apr;58(2):461–498. doi: 10.1152/physrev.1978.58.2.461. [DOI] [PubMed] [Google Scholar]
- Isenberg G. Cardiac Purkinje fibres: [Ca2+]i controls steady state potassium conductance. Pflugers Arch. 1977 Oct 19;371(1-2):71–76. doi: 10.1007/BF00580774. [DOI] [PubMed] [Google Scholar]
- Kodama I., Boyett M. R. Regional differences in the electrical activity of the rabbit sinus node. Pflugers Arch. 1985 Jul;404(3):214–226. doi: 10.1007/BF00581242. [DOI] [PubMed] [Google Scholar]
- Kodama I., Kondo N., Shibata S. Electromechanical effects of okadaic acid isolated from black sponge in guinea-pig ventricular muscles. J Physiol. 1986 Sep;378:359–373. doi: 10.1113/jphysiol.1986.sp016224. [DOI] [PMC free article] [PubMed] [Google Scholar]
- New W., Trautwein W. Inward membrane currents in mammalian myocardium. Pflugers Arch. 1972;334(1):1–23. doi: 10.1007/BF00585997. [DOI] [PubMed] [Google Scholar]
- Noble D. The surprising heart: a review of recent progress in cardiac electrophysiology. J Physiol. 1984 Aug;353:1–50. doi: 10.1113/jphysiol.1984.sp015320. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noma A., Irisawa H. Effects of calcium ion on the rising phase of the action potential in rabbit sinoatrial node cells. Jpn J Physiol. 1976;26(1):93–99. doi: 10.2170/jjphysiol.26.93. [DOI] [PubMed] [Google Scholar]
- Noma A., Kotake H., Irisawa H. Slow inward current and its role mediating the chronotropic effect of epinephrine in the rabbit sinoatrial node. Pflugers Arch. 1980 Oct;388(1):1–9. doi: 10.1007/BF00582621. [DOI] [PubMed] [Google Scholar]
- Noma A., Peper K., Trautwein W. Acetylcholine-induced potassium current fluctuations in the rabbit sino-atrial node. Pflugers Arch. 1979 Sep;381(3):255–262. doi: 10.1007/BF00583257. [DOI] [PubMed] [Google Scholar]
- Noma A., Yanagihara K., Irisawa H. Inward current of the rabbit sinoatrial node cell. Pflugers Arch. 1977 Nov 25;372(1):43–51. doi: 10.1007/BF00582205. [DOI] [PubMed] [Google Scholar]
- Ozaki H., Ishihara H., Kohama K., Nonomura Y., Shibata S., Karaki H. Calcium-independent phosphorylation of smooth muscle myosin light chain by okadaic acid isolated from black sponge (Halichondria okadai). J Pharmacol Exp Ther. 1987 Dec;243(3):1167–1173. [PubMed] [Google Scholar]
- Ozaki H., Kohama K., Nonomura Y., Shibata S., Karaki H. Direct activation by okadaic acid of the contractile elements in the smooth muscle of guinea-pig taenia coli. Naunyn Schmiedebergs Arch Pharmacol. 1987 Mar;335(3):356–358. doi: 10.1007/BF00172811. [DOI] [PubMed] [Google Scholar]
- Reuter H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature. 1983 Feb 17;301(5901):569–574. doi: 10.1038/301569a0. [DOI] [PubMed] [Google Scholar]
- Seyama I. Characteristics of the rectifying properties of the sino-atrial node cell of the rabbit. J Physiol. 1976 Feb;255(2):379–397. doi: 10.1113/jphysiol.1976.sp011285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shibata S., Ishida Y., Kitano H., Ohizumi Y., Habon J., Tsukitani Y., Kikuchi H. Contractile effects of okadaic acid, a novel ionophore-like substance from black sponge, on isolated smooth muscles under the condition of Ca deficiency. J Pharmacol Exp Ther. 1982 Oct;223(1):135–143. [PubMed] [Google Scholar]
- Shibata S. Unique vasocontraction of okadaic acid isolated from black sponge, independent of extracellular Ca2+. Blood Vessels. 1987;24(3):104–107. doi: 10.1159/000158679. [DOI] [PubMed] [Google Scholar]
- Strauss H. C., Prystowsky E. N., Scheinman M. M. Sino-atrial and atrial electrogenesis. Prog Cardiovasc Dis. 1977 Mar-Apr;19(5):385–404. doi: 10.1016/0033-0620(77)90017-2. [DOI] [PubMed] [Google Scholar]
- Tsien R. W. Calcium channels in excitable cell membranes. Annu Rev Physiol. 1983;45:341–358. doi: 10.1146/annurev.ph.45.030183.002013. [DOI] [PubMed] [Google Scholar]
- Yanagihara K., Noma A., Irisawa H. Reconstruction of sino-atrial node pacemaker potential based on the voltage clamp experiments. Jpn J Physiol. 1980;30(6):841–857. doi: 10.2170/jjphysiol.30.841. [DOI] [PubMed] [Google Scholar]