Dual regulation of cation‐selective channels by muscarinic and alpha 1‐adrenergic receptors in the rabbit portal vein.

Abstract

SUMMARY1. The excitatory actions of phenylephrine (Phe) and acetylcholine (ACh) on the smooth muscle of rabbit portal vein were investigated and compared by using wholecell and single channel configurations of the patch clamp technique, in combination with a modified concentration jump method.2. At negative holding potentials with KCl (0-1 mm EGTA) electrodes, rapid applications of Phe (> 1 JtM) and ACh (> 10 /tM) both resulted in biphasic responses consisting of fast outward or inward currents and a long-lasting inward current with an increased noise level. 3. The slow inward current was still recorded when the cell was dialysed with caesium aspartate solution complemented with 10 mm EGTA, in order to eliminate contributions of calcium-dependent conductances (K+ and Cl-currents). Phe was more potent at activating the current than ACh. Ion replacement experiments revealed that both the Phe-and ACh-induced slow inward currents are cationselective conductances (CS currents).4. The I-V relationships of the Phe-or ACh-induced CS currents were similar both for the instantaneous peak and the steady state. The tail current analysis over a wide range of membrane potentials (-150 to + 100 mV) showed that depolarizations to very positive potentials (>+ 50 mV) from near the resting membrane potential (-40 mV) can produce a several-fold increase in the steady-state activation of the CS currents, but the maximal activations were in most cases not observed even at + 100 mV. 44 ims, respectively). In addition, the relative open probability (P.,rel) was no more than 0 2 in the voltage range of -100 to -30 mV for both 50 Jm Phe and 500 ,UM ACh, suggesting low open probabilities of the Phe-and ACh-activated CS channels near the resting membrane potential.7. The activation of the CS current by 100,am Phe was completely inhibited by application of 10 UM prazosin but not affected by that of aUM atropine, while the opposite results were observed for the CS currents activated by 100 /M ACh.8. From these results, we concluded that both the ax-adrenergic and muscarinic receptor regulate a common CS channel, and this may in part be responsible for the excitatory cholinergic and adrenergic actions in the rabbit portal vein.

ACh-induced depolarization in inner ear artery is generated by activation of a TRP-like non-selective cation conductance and inactivation of a potassium conductance

“…6), which is consistent with the report that the ACh-activated single channel has a very low open probability in physiological voltage range even with a very high agonist concentration (ACh 500 μM, Inoue et al, 1993). This is not surprising because the single VSMC has a high R input (3-10 GΩ in dispersed VSMCs, Hirst et al, 1989;Wang et al, 1993)).…”

Cyclic AMP-mediated inhibition of noradrenaline-induced contraction and Ca2+ influx in guinea-pig vas deferens

“…Our data are supported by a previous study in rat portal vein, using simultaneous recordings obtained with the patch clamp and the Ca¥ fluorescence techniques, which indicated that NAinduced sustained increases in [Ca¥]é are maintained by a Ca¥ influx that is independent of voltage-dependent Ca¥ channels (Pacaud et al 1992). Inoue & Kuriyama (1993) also reported that muscarinic and á1-adrenoceptor stimulation induced the activation of nifedipine-insensitive Ca¥-permeable channels with a single channel conductance of around 25 pS in the rabbit portal vein. Their data suggest that this NA-activated Ca¥ permeable channel is non-inactivated so long as a stimulant is present.…”

Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces the change of calcium mobilization via TRPC ion channels in cultured human corporal smooth muscle cells

“…The I-V relationship of PE-induced current was linear with outward rectification at the positive potential than þ 50 mV and which was similar to the results of the previous report. 15 The PE-induced current was also suppressed by replacing extracellular monovalent cations with 140 mM NMDG, indicating the activation of NSCC.…”

“…25,26 TRPC6 was suggested as a molecular candidate for NSCC activated by GPCR in vascular smooth muscle cells. 15,27 TRPC6 is also a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells. 27 In human corporal smooth muscle cells, LPC might also bind to GPCR, GPR4 or G2A, and activate TRPC6.…”

“…It was reported that a 1 -adrenoceptor activates NSCCs permeable to Ca 2 þ in rabbit portal Lysophosphatidylcholine and calcium mobilization I So et al veins. [15][16][17] Since penile corporal myocytes also belong to the group of vascular smooth muscle cells, we examined whether similar NSCC current is elicited by PE, a 1 -adrenoceptor agonist.…”