Time Course of the Initial [Ca 2+] i Response to Extracellular ATP in Smooth Muscle Depends on [Ca 2+] e and ATP Concentration

• Published in: Biophysical journal 1998-10, Vol.75 (4), p.2050-2058
• Main Authors: Mahoney, My G., Slakey, Linda L., Benham, Christopher D., Gross, David J.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Adenosine Triphosphate - pharmacology; Animals; AORTA; ARTERE; ARTERIAS; ARTERIES; CALCIO; CALCIUM; Calcium - metabolism; Calcium - pharmacology; CATION; CATIONES; CATIONS; Cells, Cultured; CERDO; ELECTROPHYSIOLOGY; ION; ION TRANSPORT; IONES; IONS; Kinetics; Membrane Potentials - drug effects; Membrane Potentials - physiology; Patch-Clamp Techniques; PORCIN; SWINE; Time Factors; Tunica Media - cytology; Tunica Media - drug effects; Tunica Media - physiology
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(98)77647-7

In response to extracellular application of 50 μM ATP, all individual porcine aortic smooth muscle cells respond with rapid rises from basal [Ca 2+] i to peak [Ca 2+] i within 5 s. The time from stimulus to the peak of the [Ca 2+] i response increases with decreasing concentration of ATP. At ATP concentrations of 0.5 μM and below, the time to the [Ca 2+] i peak varies more significantly from cell to cell than at higher concentrations, and each cell shows complicated initiation and decay kinetics. For any individual cell, the lag phase before a response decreases with increasing concentration of ATP. An increase in lag time with decreasing ATP concentration is also observed in the absence of extracellular Ca 2+, but the lag phase is more pronounced, especially at concentrations of ATP below 0.5 μM. Whole-cell patch-clamp electrophysiology shows that in porcine aortic smooth muscle cells, ATP stimulates an inward current carried mainly by Cl − ion efflux with a time course similar to the [Ca 2+] i changes and no detectable current from an ATP-gated cation channel. A simple signal cascade initiation kinetics model, starting with nucleotide receptor activation leading to IP 3-mediated Ca 2+ release from IP 3-sensitive internal stores, fits the data and suggests that the kinetics of the Ca 2+ response are dominated by upstream signal cascade components.