title: Ca2+ channel activation and membrane depolarization mediated by Cl- channels in response to noradrenaline in vascular myocytes.
abstract: 1. 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 17 pS and 8 pS 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 -50 mV, 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 Ca(2+)-concentration ([Ca2+]i) with Indo-1 indicated that NA increased [Ca2+]i at a holding potential of -50 mV and evoked a Ca(2+)-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 ryanodine 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.
authors.affiliation: Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, INSERM CJF 88-13, Bordeaux, France.
authors.forename: P
authors.initials: P
authors.lastname: Pacaud
authors.forename: G
authors.initials: G
authors.lastname: Loirand
authors.forename: A
authors.initials: A
authors.lastname: Baron
authors.forename: C
authors.initials: C
authors.lastname: Mironneau
authors.forename: J
authors.initials: J
authors.lastname: Mironneau
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009467:Neuromuscular Depolarizing Agents; D002118:Calcium; D009638:Norepinephrine