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Electrical effects of okadaic acid extracted from black sponge on rabbit sinus node
Author(s) -
Kondo Noriaki,
Kodama Itsuo,
Kotake Hiroshi,
Shibata Shoji
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12694.x
Subject(s) - okadaic acid , verapamil , chemistry , medicine , endocrinology , biophysics , patch clamp , electrophysiology , calcium , phosphatase , biology , biochemistry , enzyme
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 × 10 −5 m ) caused a shortening of cycle length of spontaneous firing (SPCL) accompanied by increases in both maximum upstroke velocity at phase 0 and amplitude of action potential. 3 All of the effects of okadaic acid were relatively well preserved in a low‐Ca 2+ medium (0.12 m m ). Okadaic acid restored the spontaneous activity of sinus node pacemaker cells even in a Ca 2+ ‐deficient medium. 4 The effects of okadaic acid were markedly inhibited or abolished in a low Na + medium (24 m m or 70 m m ) 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 × 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 (I si ) through verapamil‐sensitive Ca 2+ channels.