Single ionic channels induced by palytoxin in guinea‐pig ventricular myocytes

Abstract

1Mechanisms of palytoxin-induced ion permeability were examined in isolated single ventricular cells of guinea-pig under whole-cell-attached patch clamp conditions. 2 Palytoxin (1-2 x 10-1 M, dissolved in Tyrode solution and put in the patch electrode) induced an elementary current flowing through single channels. Direction of the current was inward and the amplitude was 0.65 + 0.03 pA (mean + s.e. mean) at the resting membrane potential. The amplitude increased linearly with membrane hyperpolarization and decreased with depolarization; the single channel conductance was 9.5 + 0.5 pS. 3 Palytoxin-induced single channel current was resistant to tetrodotoxin (5 x 10-5M) or cobalt ions (2 x 10-3M) and was observed under Ca-free conditions. However, no channel current was induced by palytoxin (10 1-10-9 M) dissolved in Na+-free, choline-Tyrode solution. 4 Palytoxin also induced single channel currents in Na+-free, NH+-, Li+-or Cs+-Tyrode solution, and the slope conductances were 16.5 + 1.6 pS, 9.2 + 0.7 pS and 11.0 + 0.7 pS, respectively.5 These results indicate that palytoxin forms a new type of ionic channel with unique ion selectivity and gating behaviour.

Palytoxin disrupts cardiac excitation-contraction coupling through interactions with P-type ion pumps

“…In line with the observations in ventricular myocytes (2,20,27,35), we found that palytoxin generated a very similar current in atrial myocytes. In particular, the palytoxin-induced current displayed a linear I-V relationship that was reversed at ϳ5 mV, was comparable in magnitude, and could be antagonized by cardiac glycosides.…”

“…In mammalian ventricular myocytes, palytoxin induces opening of nonselective cation channels permeable to Na ϩ and K ϩ by converting the Na ϩ -K ϩ pump into a channel (2,20,27,35). At negative holding potentials, the palytoxininduced inward current is carried mainly by Na ϩ and can be inhibited by cardiac glycosides (27).…”

“…Palytoxin binds to the Na ϩ -K ϩ pump and converts it into a nonselective cation channel (26). The palytoxin-induced current through this channel was characterized previously in ventricular myocytes (20,27,35). In addition, a more recent study revealed detailed insights into the molecular mechanism of palytoxin action on the Na ϩ -K ϩ pump (2,17).…”

Palytoxin acidifies chick cardiac cells and activates the Na+/H+ antiporter

“…1, left panel). This pathway could be the non-selective cationic channel that has recently been shown to be activated by PTX in rat cardiomyocytes [29,30] and for which no inhibitor is yet available. The question whether the same channel is responsible for the increased H+ and ethylisopropylamilorideinsensitive Na+ transports cannot be answered easily for unitary H+ currents are too small to be detected in patch clamp recordings.…”

Developmental Biology of Neoplastic Growth

“…The following lines of evidence established that PTX interacts with the Na + / K + pump itself: (1) PTX induced ouabain-sensitive cation flux in yeast cells (which lack endogenous Na + /K + pumps) just after the expression of both Na + /K + -ATPase α-and β-subunits, and not of either subunit alone (Scheiner-Bobis et al 1994) (2) incorporation of in vitro-translated Na + /K + -ATPase α-and β-subunits into lipid bilayers allowed PTX to open cation channels with a unitary conductance of about 7 pS (Hirsh and Wu 1997) similar to that of the relatively nonselective channels opened by PTX in various excitable tissues Ikeda et al 1988;Muramatsu et al 1988;Rakowski et al 2007). …”