Figure 2: Human TPC1 is a voltage-dependent sodium channel.
From: The human two-pore channel 1 is modulated by cytosolic and luminal calcium
(a) Whole-vacuole currents recorded in the presence of 90 nM PI(3,5)P2 in standard symmetrical 100 mM-NaCl condition. MgCl2 2 mM was present in the cytosolic bath solution. Currents were elicited by 1 sec-voltage pulses from −80 to +90 mV, in 10 mV-increments. Holding potential of −70 mV. (b) Same vacuole as in a, but bath (cytosolic) NaCl concentration was decreased to 10 mM (in the presence of 90 nM PI(3,5)P2). (c) Current–voltage relationships of PI(3,5)P2-evoked hTPC1 currents in the presence of 200 mM NaCl (n = 4), 100 mM (n = 8) or 10 mM (n = 4) in the bath. For each vacuole, current amplitudes evoked by 90 nM PI(3,5)P2 were normalized to the value at +40 mV in 100 mM NaCl-condition. (d) Effect of cytosolic magnesium on hTPC1 currents recorded at positive voltages. Currents were normalised to the value at +90 mV. We fitted the data, continuous lines, with the following equation: I0(V)/([Mg2+]/KMg exp(2δFV/RT)), where I0(V) was the linear fit of the current in the absence of cytosolic Mg2+. (e) Plot of reversal voltages versus cytosolic NaCl activity. Data were shown as mean ± standard deviation. The solid line represents the theoretical Nernst voltage for sodium.
