Abstract
cAMP-gated channels were studied in inside-out membrane patches excised from the apical cellular pole of isolated olfactory receptor cells of the rat. In the absence of divalent cations the dose-response curve of activation of patch current by cAMP had a KM of 4.0 microM at -50 mV and of 2.5 microM at +50 mV. However, addition of 0.2 or 0.5 mM Ca2+ shifted the KM of cAMP reversibly to the higher cAMP concentrations of 33 or 90 microM, respectively, at -50 mV. Among divalent cations, the relative potency for inducing cAMP affinity shifts was: Ca2+ > Sr2+ > Mn2+ > Ba2+ > Mg2+, of which Mg2+ (up to 3 mM) did not shift the KM at all. This potency sequence corresponds closely to that required for the activation of calmodulin. However, the Ca(2+)-sensitivity is lower than expected for a calmodulin-mediated action. Brief (60 s) transient exposure to 3 mM Mg2+, in the absence of other divalent cations, had a protective effect in that following washout of Mg2+, subsequent exposure to 0.2 mM Ca2+ no longer caused affinity shifts. This protection effect did not occur in intact cells and was probably a consequence of patch excision, possibly representing ablation of a regulatory protein from the channel cyclic nucleotide binding site. Thus, the binding of divalent cations, probably via a regulatory protein, controls the sensitivity of the cAMP-gated channels to cAMP. The influx of Ca2+ through these channels during the odorant response may rise to a sufficiently high concentration at the intracellular membrane surface to contribute to the desensitization of the odorant-induced response. The results also indicate that divalent cation effects on cyclic nucleotide-gated channels may depend on the sequence of pre-exposure to other divalent cations.
Highlights
The stimulation of olfactory receptor neurons by odorants results in the formation of cAMP, which directly gates cation-conducting membrane ion channels, leading to membrane depolarization and spike initiation
We describe the inhibitory effects of divalent cations on cAMP-gated channels from olfactory cells of the rat
There was no significant difference in the sensitivity to cAMP
Summary
The stimulation of olfactory receptor neurons by odorants results in the formation of cAMP, which directly gates cation-conducting membrane ion channels, leading to membrane depolarization and spike initiation (for a review, see Reed, 1992). Dr Lynch's present address is Garvan Institute of Medical Research, St Vincents Hospital, 384 Victoria St, Darlinghurst, New South Wales 2010, Australia. Address reprint requests and correspondence to Dr B. THE JOURNALor GENEgALeHVSlOLO(;V- VOLUME103 1994 continuous odorant exposure, odorant-induced responses usually display a progressive attenuation, or desensitization. The mechanisms involved in this process have not yet been clearly elucidated, yet are crucial to the understanding of olfactory transduction because desensitization, by modulating the time-dependence of neuronal firing patterns, contributes to the coding of odor information (Kauer, 1987)
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