Mitochondrial inhibitors activate influx of external Ca(2+) in sea urchin sperm.
Sea urchin sperm have a single mitochondrion which, aside from its main ATP generating function, may regulate motility, intracellular Ca(2+) concentration ([Ca(2+)](i)) and possibly the acrosome reaction (AR). We have found that acute application of agents that inhibit mitochondrial function via differing mechanisms (CCCP, a proton gradient uncoupler, antimycin, a respiratory chain inhibitor, oligomycin, a mitochondrial ATPase inhibitor and CGP37157, a Na(+)/Ca(2+) exchange inhibitor) increases [Ca(2+)](i) with at least two differing profiles. These increases depend on the presence of extracellular Ca(2+), which indicates they involve Ca(2+) uptake and not only mitochondrial Ca(2+) release. The plasma membrane permeation pathways activated by the mitochondrial inhibitors are permeable to Mn(2+). Store-operated Ca(2+) channel (SOC) blockers (Ni(2+), SKF96365 and Gd(2+)) and internal-store ATPase inhibitors (thapsigargin and bisphenol) antagonize Ca(2+) influx induced by the mitochondrial inhibitors. The results indicate that the functional status of the sea urchin sperm mitochondrion regulates Ca(2+) entry through SOCs. As neither CCCP nor dicycloexyl carbodiimide (DCCD), another mitochondrial ATPase inhibitor, eliminate the oligomycin induced increase in [Ca(2+)](i), apparently oligomycin also has an extra mitochondrial target.
Ardón
F
F
Departamento de Biofísica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Distrito Federal, 04510, México.
Rodríguez-Miranda
E
E
Beltrán
C
C
Hernández-Cruz
A
A
Darszon
A
A
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002412:Cations; D002998:Clonazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D005682:Gadolinium / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology; D009840:Oligomycins / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D012617:Sea Urchins / Q000187:drug effects / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D013094:Spermatozoa / Q000378:metabolism*; D013841:Thiazepines / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002412:Cations; D007093:Imidazoles; D009840:Oligomycins; D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; D014475:Uncoupling Agents; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D002998:Clonazepam; D000968:Antimycin A; C079032:CGP 37157; D009532:Nickel; D005682:Gadolinium; D006180:Proton-Translocating ATPases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium