Effects of diuretics on GABA‐gated chloride current in frog isolated sensory neurones

Abstract

Effects of three diuretics (furosemide, amiloride and α‐human atrial natriuretic polypeptide (α‐hANP)) on GABA‐activated chloride current (ICl) were investigated in frog isolated sensory neurones, following suppression of Na+, K+ and Ca2+ currents, by use of a ‘concentration‐clamp’ technique. Furosemide inhibited the GABA‐activated ICl in a non‐competitive manner and facilitated the inactivation phase, while amiloride inhibited the GABA response in a competitive manner, both inhibitions being concentration‐dependent. α‐hANP had no effects on the GABA‐induced ICl. The reversal potential of GABA‐activated ICl (EGABA) was not shifted in the presence of amiloride or furosemide. The results suggest that amiloride may act at the GABA binding site while furosemide may act on the GABA‐gated chloride channel.

Amiloride Inhibition of γ-Aminobutyric AcidAReceptors Depends upon the α Subunit Subtype

“…We found that amiloride inhibited the activity of recombinant GABARs of mammalian origin, confirming an earlier report with GABARs in frog sensory neurons (Inomata et al, 1988). Amiloride has also been shown to modulate the activity of neurotransmitter receptors, including the adenosine (Garritsen et al, 1990) and adrenergic receptors (Howard et al, 1987;Nunnari et al, 1987).…”

“…The results of Inomata et al (1988) suggested that amiloride was a competitive antagonist at GABARs in frog sensory neurons. Therefore, we examined the effect of GABA concentration on inhibition of the ␣6␤3␥2L receptor by amiloride.…”

“…The diuretics amiloride and furosemide were first reported to inhibit the activity of GABARs in frog sensory neurons (Inomata et al, 1988). The activity of furosemide was subsequently found to depend upon the ␣ and ␤ subtype composition of receptor, with ␣6␤2/3-containing receptors being 20-to 100-fold more sensitive to furosemide than receptors containing other ␣ subtypes (Korpi et al, 1995;Thompson et al, 1999).…”

Effects of furosemide on the resting membrane potentials and the transmitter-induced responses of the Aplysia ganglion cells.

“…They all concluded that FM had a specific depressing effect on the receptor-operated opening of Cl--channels in these neurons. Inomata et al (1988) investigated the effects of FM on the GABA-activated chloride current (Ic1) of the isolated frog sensory neurons, using so called concen tration clamp method. They reported that FM inhibited the GABA-activated Ic1, in a non-competitive manner, and suggested that FM would act specifically on the open channel conformation of the GABA-gated Cl--channel and facilitate its inactivation.…”

Amiloride and GMQ Allosteric Modulation of the GABA-A ρ1 Receptor: Influences of the Intersubunit Site

“…Furthermore, guanidine compounds that modulate the acid-sensing ion channel influence Cys-loop receptor activity. The inhibitory effect of the diuretic amiloride, an acid-sensing ion channel antagonist, on GABA-A receptors was first reported in the frog sensory neurons (Inomata et al, 1988), and subsequent studies focused on amiloride in GABA-A abg receptors showed that the guanidine compound competitively antagonized the receptors with a 10-fold increased potency in GABA-A a6-containing receptors (Fisher, 2002). In the inhibitory glycine receptor, amiloride exhibited competitive antagonism in receptors expressed in rat spinal neurons and inferior colliculus (Li et al, 2003a,b;Tang et al, 2006).…”