Effects of inositol phosphates on the membrane activity of smooth muscle cells of the rabbit portal vein

The effects of intracellular perfusion of inositol 1,4,5-trisphosphate (InsP₃) or inositol 1,3,4,5-tetrakisphosphate (InsP₄) on electrical responses of smooth muscle cell membranes of the rabbit portal vein were studied using the whole cell voltage clamp technique. Depolarisation to 0 mV from a holding potential of -60 mV, evoked inward Ca (I_Ca), transient outward (I_TO), oscillatory outward (I_OO) and sustained outward (I_SO) currents. Generation of I_OO was dependent on the [Ca]_o, but it was also generated in 0 mM Ca solution for over 10 min. Form amplitude histograms, I_OO was divided into two components. Reduction in [Ca]_o inhibited the appearance of but not the amplitudes of both I_OO components. However, the larger component of I_OO was more resistant to a reduction in [Ca]_o than the smaller one. InsP₃ (10 μM) increased the frequency of both I_OO components to a greater extent than their amplitude, but the larger component was more sensitive to InsP₃ than the smaller one. The increase in the occurrence of I_OO induced by InsP₃ did not occur following pretreatment with 3 mM caffeine or 1 nM A23187. In normal PSS, InsP₃ was evoked by a depolarising pulse positive to -40 mV, whereas following perfusion with InsP₃ (10 μM), I_OO was evoked at -60 mV. In normal PSS, intracellular perfusion with 10 μM InsP₄ changed neither the frequency nor the amplitude of I_OO, and the amplitudes of I_Ca, I_TO and I_SO were also unchanged. However, in 10 mM Ca solution, 10 μM InsP₄ generated I_OO at a membrane potential of -60 mV. It is concluded that InsP₃ activates I_OO in smooth muscle cell membranes of the rabbit portal vein by causing an increase in intracellular Ca by facilitating Ca release from the storage sites. In 10 mM Ca solution, InsP₄ also accelerates the generation of I_OO, and it is possible that this effect is mediated by inositol 1,3,4-trisphosphate, a metabolite of InsP₄ rather than by InsP₄ itself.