Ca²⁺ channel activation and membrane depolarization mediated by Cl⁻ channels in response to noradrenaline in vascular myocytes

Abstract

I 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 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.

Chloride channel blockers inhibit myogenic tone in rat cerebral arteries

“…Other investigators have suggested that certain agonists activate chloride channels in vascular smooth muscle. For instance, noradrenaline-induced contractions of rat portal vein are inhibited by 9-anthracene chloride (Pacaud et al 1991), a blocker of various types of chloride channels (Large & Wang, 1996). Endothelin-, noradrenaline-, and angiotensin II-induced constrictions of renal arterioles are inhibited by IAA_94 (Carmines, 1995;Takenaka, Kanno, Kitamura, Hayashi, Suzuki & Saruta, 1996).…”

Effects of the novel potassium channel opener, UR‐8225, on contractile responses in rat isolated smooth muscle

“…Since this tonic contraction was generated in the presence of methoxyverapamil, it can be concluded that the inhibitory effect of UR-8225 and levcromakalim on K+ conductance does not require the entry of Ca2" through dihydropyridine-sensitive channels (Kreye & Weston, 1986). The inhibitory effect on noradrenaline-induced tonic contractions can be explained because noradrenaline increases open state-probability of single voltage-activated Ca2" channels (Nelson et al, 1988;Pacaud et al, 1991), whereas K+ channel openers oppose this action by hyperpolarizing the membrane potential (Hamilton et al, 1986;Bray et al, 1991). Other possible explanations are that the hyperpolarization induced by UR-8225 and levcromakalim may inhibit the ability of depleted intracellular Ca2" stores to refill after Ca2" release has occurred and/or the synthesis of inositol 1,4,5-trisphosphate (IP3)-induced by noradrenaline.…”

Relation between α1‐adrenoceptor subtypes and noradrenaline‐induced contraction in rat portal vein smooth muscle

“…The MIA-adrenoceptor subtype has been shown to gate Ca2" influx, sometimes through L-type Ca2+ channels but it has also been reported that the a 1A-adrenoceptor subtype could stimulate the formation of inositol phosphates (Han et al, 1990). In portal vein smooth muscle, the sequence of events induced by noradrenaline can be summarized as follows: (i) noradrenaline releases intracellular Ca2+ stores through InsP3 production; (ii) the calcium released opens chloride channels producing outward chloride current and membrane depolarization (Byrne & Large, 1988); (iii) this depolarization produces Ca2+ entry through voltagedependent Ca2+ channels; (iv) the open probability of Ca2+ channels is enhanced by noradrenaline (Pacaud et al, 1991). As activation of the alL-adrenoceptor subtype alone is unable to elicit contraction, these results suggest that both (XIL-and OClN-adrenoceptors mediate the noradrenaline-induced contraction in physiological conditions.…”