@article {Nuttle753, author = {L C Nuttle and J M Farley}, title = {Frequency modulation of acetylcholine-induced oscillations in Ca++ and Ca(++)-activated Cl- current by cAMP in tracheal smooth muscle.}, volume = {277}, number = {2}, pages = {753--760}, year = {1996}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The effects of adenosine 3{\textquoteright}:5{\textquoteright}-cyclic monophosphate (cAMP) on acetylcholine (ACh)-induced oscillations in intracellular calcium concentration ([Ca++]i) and Ca(++)-activated Cl- current (ClCa current) were determined in isolated tracheal smooth muscle cells. Whole-cell current was measured in individual smooth muscle cells with patch clamp methodology. At a holding potential of -80 mV, ACh (0.1 microM) elicits base line-separated oscillations in ClCa current which correlate with oscillations in [Ca++]i. The addition of the beta adrenoceptor agonist isoproterenol (ISO) (10 nM to 1 microM) in the continued presence of ACh caused a concentration-dependent decrease in the frequency of the oscillations in ClCa current with significant reductions in oscillation frequency of 21.4 and 81.5\% in the presence of 0.01 and 0.1 microM ISO, respectively (P \< .05). This effect was mimicked by both forskolin (FSK) (3 microM) and 3-isobutyl-1-methylxanthine (IBMX) (30 microM). ISO and forskolin also inhibited ACh-induced oscillations in [Ca++]i measured by confocal fluorescence microscopy in non-voltage-clamped cells loaded with the Ca(++)-sensitive dye, fluo3. The inhibition of ACh-induced oscillations in ClCa current by ISO was partially reversed by increasing extracellular Ca++. These data are consistent with previous observations that the frequency of ACh-induced oscillations in [Ca++]i and ClCa current is dependent on the concentration of extracellular Ca++ and the influx of Ca++ through a verapamil-sensitive pathway. Moreover, these results lend support to the hypothesis that beta adrenoceptors inhibit the ACh-induced increase in [Ca++]i through a cAMP-dependent mechanism that inhibits Ca++ influx and in independent of changes in membrane potential.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/277/2/753}, eprint = {https://jpet.aspetjournals.org/content/277/2/753.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }