Multiple pathways responsible for the stretch-induced increase in Ca super(2+) concentration in toad stomach smooth muscle cells

• Published in: The Journal of physiology 2000-04, Vol.524 (1), p.3-17
• Main Authors: Kirber, M T, Guerrero-Hernandez, A, Bowman, D S, Fogarty, KE, Tuft, R A, Singer, J J, Fay, F S
• Format: Article
• Language: English
• Subjects: Bufonidae
• ISSN: 0022-3751

A digital imaging microscope with fura-2 as the Ca super(2+) indicator was used to determine the sources for the rise in intracellular calcium concentration ([Ca super(2+)] sub(i)) that occurs when the membrane in a cell-attached patch is stretched. Unitary ionic currents from stretch-activated channels and [Ca super(2+)] sub(i) images were recorded simultaneously. When suction was applied to the patch pipette to stretch a patch of membrane, Ca super(2+)-permeable cation channels (stretch-activated channels) opened and a global increase in [Ca super(2+)] sub(i) occurred, as well as a greater focal increase in the vicinity of the patch pipette. The global changes in [Ca super(2+)] sub(i) occurred only when stretch-activated currents were sufficient to cause membrane depolarization, as indicated by the reduction in amplitude of the unitary currents. When Ca super(2+) was present only in the pipette solution, just the focal change in [Ca super(2+)] sub(i) was obtained. This focal change was not seen when the contribution from Ca super(2+) stores was eliminated using caffeine and ryanodine. These results suggest that the opening of stretch-activated channels allows ions, including Ca super(2+), to enter the cell. The entry of positive charge triggers the influx of Ca super(2+) into the cell by causing membrane depolarization, which presumably activates voltage-gated Ca super(2+) channels. The entry of Ca super(2+) through stretch-activated channels is also amplified by Ca super(2+) release from internal stores. This amplification appears to be greater than that obtained by activation of whole-cell Ca super(2+) currents. These multiple pathways whereby membrane stretch causes a rise in [Ca super(2+)] sub(i) may play a role in stretch-induced contraction, which is a characteristic of many smooth muscle tissues.