Ca2+ channel activation and membrane depolarization mediated by Cl- channels in response to noradrenaline in vascular myocytes.
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.
Pacaud
P
P
Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, INSERM CJF 88-13, Bordeaux, France.
Loirand
G
G
Baron
A
A
Mironneau
C
C
Mironneau
J
J
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
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009467:Neuromuscular Depolarizing Agents; D002118:Calcium; D009638:Norepinephrine