Electrical effects of okadaic acid extracted from black sponge on rabbit sinus node.
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.
Kondo
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N
Department of Pharmacology, University of Hawaii, Honolulu.
Kodama
I
I
Kotake
H
H
Shibata
S
S
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011161:Porifera; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects*; D012964:Sodium / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D004988:Ethers, Cyclic; D019319:Okadaic Acid; D001285:Atropine; D012964:Sodium; D011433:Propranolol; D014700:Verapamil; D010749:Phosphoprotein Phosphatases; D002118:Calcium