ISSN:
1432-1912
Keywords:
Key words Palytoxin
;
Cation channel
;
Na+-Ca2+
;
exchange
;
Cytosolic Ca2+
;
Dichlorobenzamil
;
Ouabain
;
Vascular smouth muscle cell
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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 μM) 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+.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00004907
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