PT  - JOURNAL ARTICLE
AU  - X Liu
AU  - J M Farley
TI  - Acetylcholine-induced Ca++-dependent chloride current oscillations are mediated by inositol 1,4,5-trisphosphate in tracheal myocytes.
DP  - 1996 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 796--804
VI  - 277
IP  - 2
4099  - http://jpet.aspetjournals.org/content/277/2/796.short
4100  - http://jpet.aspetjournals.org/content/277/2/796.full
SO  - J Pharmacol Exp Ther1996 May 01; 277
AB  - We demonstrated previously that acetylcholine (ACh) induces Ca++ oscillations in tracheal myocytes. These oscillations, as measured with fluo3-loaded cells and confocal microfluorimetry, correlated with Ca++-dependent Cl- current (Clca) oscillations measured by whole-cell voltage-clamp recording. In the current study, we investigated the role of inositol 1,4,5-trisphosphate (IP3) in ACh-induced oscillations in Ca++ and membrane currents. Both an IP3 receptor monoclonal antibody (5 micrograms/ml) and an IP3 receptor antagonist, heparin (5 mg/ml), directly introduced into the cells via the patch pipette, reduced or abolished oscillations in Clca induced by ACh. In addition, IP3 (1-100 microM) applied intracellularly, elicited concentration-dependent Clca oscillations that resembled those induced by ACh. Increasing external Ca++ concentration enhanced IP3-induced Clca oscillations, whereas verapamil (10 microM), a voltage-operated Ca++ channel blocker, attenuated IP3-induced Clca oscillations as well as both control and IP3-enhanced spontaneous transient outward currents. However, neither 5 microgram/ml IP3 receptor monoclonal antibody nor 5 mg/ml heparin altered the caffeine-induced transient Clca. Caffeine (10 mM) reversibly eliminated IP3-induced Clca oscillations as well as IP3-enhanced spontaneous transient outward currents, which indicates that caffeine releases Ca++ via a mechanism independent of the IP3 receptor. The findings are consistent with the hypothesis that ACh-induced Ca++ oscillations can arise and be sustained via IP3-induced Ca++ release pathways.