Unusual potassium channels mediate nonadrenergic noncholinergic nerve-mediated inhibition in opossum esophagus

Abstract

Field stimulation of the circular muscle of the opossum esophagus produces a transient hyperpolarization (inhibitory junction potential, IJP) followed by an "off" depolarization. A similar nonadrenergic, noncholinergic (NANC) response in guinea pig taenia caecum has been shown to be due to an increase in the potassium ion permeability of the smooth muscle cell membrane. Double sucrose gap studies showed a decrease in resistance during the IJP, and a reversal at an estimated membrane potential of about -90 mV (4 mM K+). The reversal potential was dependent on the extracellular potassium concentration, shifting to -75 mV when the potassium in the superfusion medium was increased to 10 mM. The IJP in the opossum esophageal circular smooth muscle is therefore like the IJP of the guinea pig taenia caecum in that it is probably due to a selective increase in potassium ion permeability. Potassium conductance blocking agents, tetraethylammonium chloride (TEA, 20 mM) and 4-aminopyridine (4-AP, 5 mM) both caused a depolarization of the smooth muscle cell membrane, but TEA increased the membrane resistance, whereas 4-AP did not affect the membrane conductance in a consistent way. A decrease in IJP amplitude owing to these agents was not apparent. Apamin (10 microM) did not affect the membrane potential, the membrane resistance, or the IJP. Quinine (0.1 mM) produced effects quantitatively similar to those of TEA. Quinine (1 mM) did abolish the IJP, however, this was likely due to a blockade of impulse transmission of the intramural nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasoactive intestinal polypeptide and non‐adrenergic, non‐cholinergic inhibition in lower oesophageal sphincter of opossum

“…These differed from the ij.ps recorded from body circular muscle (Daniel et al, 1983;Jury et al, 1985) in being smaller (cf: Table 2 and see Daniel et al, 1983;Jury et al, 1985) and lacking detectable after-depolarization (Figures 4 and 5). They were accompanied by a significant reduction in the magnitude of electrotonic potentials evoked by hyperpolarizing constant current pulses (Table 2 and Figure 4), indicating that there was a conductance increase.…”

“…NANC-relaxation of gut muscle, whenever it has been analysed (Tomita, 1972;Bywater et al, 1981;Jury et al, 1985) is caused by increased potassium conductance. Our earlier studies showed that none of several established Kconductance blockers (apamin, tetraethylammonium, 4-aminopyridine or quinine) abolished the ij.p.…”

“…by increasing the K+-conductance of the smooth muscle cell membrane (Daniel et al, 1983;Jury et al, 1985). In contrast, VIP caused slight or no membrane hyperpolarization accompanied by a decreased membrane conductance, followed by membrane repolarization and membrane oscillations, which triggered action potentials on the depolarizing phase (Daniel et al, 1983;.…”

Tetrodotoxin‐sensitive and ‐insensitive relaxations in the rat oesophageal tunica muscularis mucosae.

“…TEA produced a biphasic response which could be attributed to a TTX-insensitive release from nerve endings as previously suggested by Kirpekar & Prat (1978) who reported TEA-induced noradrenaline release from sympathetic nerve endings of the cat spleen. Thus, if potassium channel activation were involved in f.s.r., such channels as in the opossum lower oesophageal sphincter (Jury, Jager & Daniel, 1985) must have properties different from those demonstrated in other non-vascular smooth muscle, e.g. guinea-pig taenia coli (Mass, 1981).…”

Similarity of relaxations evoked by BRL 34915, pinacidil and field‐stimulation in rat oesophageal tunica muscularis mucosae

“…Previous attempts to test this hypothesis by the use of apamin, a specific inhibitor of certain Ca2 +-activated potassium channels (Banks et al, 1979), and tetraethylammonium (TEA), a nonselective potassium channel blocker (Hille, 1984), were unsuccessful (Akbarali et al, 1986). However, the potassium channels implicated in relaxations evoked by field stimulation may be atypical, and resemble those described in the lower oesophageal sphincter of the opossum oesophagus (Jury et al, 1985) and guinea-pig circular muscle of the intestine (Yamanaka et al, 1985), in so far as they are not involved in maintaining resting membrane potential, or generation of non-adrenergic, non-cholinergic (NANC)-nerve mediated inhibitory junctional potentials in the guinea-pig taenia coli (Den Hertog & Jager, 1975). BRL 34915 ((+ )-6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1 -pyrrolidyl)-2H-benzo (b) pyran-3-ol) and pinacidil (N"-cyano-N-4 pyridyl-N'-1,2,2-trimethylpropylguanidine), have recently been shown to open potassium channels in a number of smooth muscle preparations including guinea-pig taenia caeci (Weir & Weston, 1986a), rabbit aorta (Kreye & Weston, 1986;Cook et al, 1987;Soiitherton et al, 1987), rat uterus (Edwards et al, 1987), rat portal vein (Weir & Weston, 1986b); and rabbit mesenteric artery (Coldwell & Howlett, 1987).…”