Characteristics of palytoxin-induced cation currents and Ca2+ mobilization in smooth muscle cells of rabbit portal vein.
We examined the nature of the palytoxin (PTX)-induced channel and its relevance to the Ca2+ mobilizing effect of the toxin on smooth muscle cells isolated from rabbit portal vein using whole-cell voltage-clamp and microfluorimetric techniques. PTX (1 nM) induced a sustained, irreversible inward current at a holding potential of -40 mV. The PTX-induced current reversed at 0.5 +/- 0.6 mV, and the PTX-induced channel permitted the passage of Na+, K+, Cs+ and, to a lesser extent, Li+, but not choline+ or Ca2+. During the sustained phase of the current, superfusion of Ni2+ (5 mM), La3+ (0.5 mM) or 2,4-dichlorobenzamil (2,4-DCB, 25 microM) reduced the current amplitude and decreased the slope conductance without changing the reversal potential. In 5 of 7 experiments, ouabain transiently increased the PTX-induced inward current and shifted the reversal potential in a positive direction. Subsequently, ouabain inhibited the current in every cell. PTX (10 nM) induced a sustained rise in cytosolic Ca2+ ([Ca2+]i), which was resistant to verapamil but suppressed by omission of extracellular Ca2+. When external Na+ was replaced by choline+, PTX did not increase [Ca2+]i. Pretreatment with 2,4-DCB prevented the elevation of [Ca2+]i due to PTX. These results suggest that PTX does not directly stimulate Ca2+ entry but induces entry through Na(+)-Ca2+ exchange as a consequence of increased cytosolic Na+. Ni2+, La3+, 2,4-DCB and ouabain were shown to act as blockers of the PTX-induced channel. Ouabain may also inhibit Na+ pump current activated by cytosolic Na+.
Ishii
K
K
Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Japan.
Ikeda
M
M
Ito
K
K
D000178:Acrylamides / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology; D003064:Cnidarian Venoms; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D019831:Sodium-Calcium Exchanger; D000095702:Polyether Toxins
D000178:Acrylamides; D002118:Calcium; D002352:Carrier Proteins; D003064:Cnidarian Venoms; D007473:Ion Channels; D010042:Ouabain; D019831:Sodium-Calcium Exchanger; C010272:palytoxin; D000095702:Polyether Toxins