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 (ICa), transient outward (ITO), oscillatory outward (IOO) and sustained outward (ISO) currents. Generation of IOO was dependent on the [Ca]o, but it was also generated in 0 mM Ca solution for over 10 min. Form amplitude histograms, IOO was divided into two components. Reduction in [Ca]o inhibited the appearance of but not the amplitudes of both IOO components. However, the larger component of IOO was more resistant to a reduction in [Ca]o than the smaller one. InsP3 (10 μM) increased the frequency of both IOO 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 IOO 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), IOO was evoked at -60 mV. In normal PSS, intracellular perfusion with 10 μM InsP4 changed neither the frequency nor the amplitude of IOO, and the amplitudes of ICa, ITO and ISO were also unchanged. However, in 10 mM Ca solution, 10 μM InsP4 generated IOO at a membrane potential of -60 mV. It is concluded that InsP3 activates IOO 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 IOO, and it is possible that this effect is mediated by inositol 1,3,4-trisphosphate, a metabolite of InsP4 rather than by InsP4 itself.
All Science Journal Classification (ASJC) codes
- Clinical Biochemistry
- Physiology (medical)