Maitotoxin increases voltage independent chloride and sodium currents in GH4C1 rat pituitary cells.
Maitotoxin (MTX) is a 3,424 dalton polyether marine toxin that causes influx of calcium through type L voltage-dependent calcium channels (L-VDCC) in GH4C1 rat pituitary cells, presumably as the result of membrane depolarization. In this study we have investigated the ionic conductances responsible for MTX-induced depolarization under voltage clamp conditions using the perforated and ruptured patch methods. MTX-induced steady-state voltage independent currents of nearly 400 pS/pF within seconds of addition to the bath. Ion substitution experiments demonstrated these currents are consistent with the conductance of sodium and chloride, but not calcium, ions. MTX induction of the voltage-independent chloride conductance in GH4C1 cells occurred concurrently without modification of L-VDCC currents. Pretreatment with nimodipine eliminated voltage activation of L-VDCC, and reduced by two thirds the voltage independent current. Analysis as a function of time of MTX exposure revealed that the first 60 sec of MTX-induced currents were not affected by nimodipine pretreatment, but subsequent additional currents were prevented. This indicates that the initial currents induced by MTX occur independently of L-VDCC mediated calcium entry, but full activation of these currents by MTX likely requires the involvement L-VDCC. Taken together this work identifies a voltage-independent sodium/chloride conductance as an initial action of MTX, one that may promote the sequence of ionic events leading to activation of L-VDCC and massive calcium entry.
Young
R C
RC
Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston 29412, USA.
McLaren
M
M
Ramsdell
J S
JS
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002120:Calcium Channel Agonists / Q000633:toxicity; D002478:Cells, Cultured; D065101:Chloride Channel Agonists; D008387:Marine Toxins / Q000633:toxicity*; D035964:Oxocins; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D062687:Sodium Channel Agonists; D000095702:Polyether Toxins
D002120:Calcium Channel Agonists; D065101:Chloride Channel Agonists; D008387:Marine Toxins; D035964:Oxocins; D062687:Sodium Channel Agonists; C020394:maitotoxin; D000095702:Polyether Toxins