Activation by high potassium of a novel voltage-operated Ca2+ channel in rat spleen.
1. High potassium produced a concentration-dependent contraction in rat isolated spleen. 2. The high potassium-induced contraction of rat spleen was abolished in Ca(2+)-free Krebs solution containing 1 mM EGTA, and the subsequent addition of 3 mM Ca2+ restored the high potassium-induced contraction to the control level. 3. Nifedipine, verapamil, diltiazem, Cd2+, Ni2+, Co2+, R-(+)-Bay K 8644 and pimozide inhibited and relaxed high potassium-induced contraction of rat spleen with IC50 and EC50 values much higher than those values in rat aorta. 4. In addition, high potassium-stimulated contraction of rat spleen was insensitive to omega-conotoxin GVIA, omega-conotoxin MVIIC and omega-agatoxin IVA. 5. The high potassium-induced contraction of rat spleen was also unaffected by tetrodotoxin (TTX), prazosin, chloroethylclonidine (CEC), yohimbine, propranolol, atropine, diphenhydramine, cimetidine, ketanserin, 3-tropanyl-indole-3-carboxylate, saralasin, indomethacin, nordihydroguaiaretic acid, GR32191B, domperidone, naloxone, chlorpromazine, suramin, (+/-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione (DNQX), L-659,877, L-703,606, lorglumide, PD 135,158 N-methyl-D-glucamine, benextramine, amiloride, dantrolene, TMB-8, econazole, staurosporine and neomycin. 6. Forskolin and sodium nitroprusside relaxed high potassium-induced contraction of rat spleen with EC50 values of 0.55 +/- 0.04 and 20.0 +/- 2.7 microM, respectively. 7. It is concluded that high potassium may activate a novel, pharmacologically uncharacterized voltage-operated Ca2+ channel in rat spleen.
Ko
F N
FN
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Huang
S Y
SY
Teng
C M
CM
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011188:Potassium