Ca2+ channel activation and membrane depolarization mediated by Cl− channels in response to noradrenaline in vascular myocytes
Résumé
The effects of noradrenaline (NA) were studied on vascular smooth muscle cells isolated from rat portal vein. 2 Two types of single-Ca2+ channel currents with conductances of 17pS and 8pS were obtained in cell-attached configuration. Bath application of NA increased the open probability of both channels during depolarizing pulses without a change of background membrane conductance. However, NA did not open Ca2 + channels when the membrane patch potential was held at-50mV, which is about the resting potential in physiological conditions. 3 In the whole-cell configuration, studies of voltage-dependent Ca2+ channel currents showed that the peak conductance curve was not shifted to more negative potentials by NA. 4 Measurements of internal Ca2+-concentration ([Ca2+]) with Indo-1 indicated that NA increased [Ca2+] at a holding potential of-50 mV and evoked a Ca2 '-activated Cl-current. These effects were blocked when heparin was included in the pipette solution. 5 A Cl-channel blocker without effect on Ca2 + channels (anthracene-9-carboxylic acid) inhibited the contractions of portal vein strips induced by NA in a manner similar to that produced by a Ca2 + channel inhibitor (isradipine). The NA-induced contraction was completely suppressed in the presence of ryano-dine which depletes intracellular Ca2 + stores. 6 The present study suggests that activation of Cl-channels by Ca2+ release produces a membrane depolarization which is a prerequisite for enhanced opening of voltage-dependent Ca2+ channels in response to NA in venous smooth muscle.