Stretch-activated ion channels in smooth muscle: a mechanism for the initiation of stretch-induced contraction

Abstract

As in many smooth muscle tissue preparations, single smooth muscle cells freshly dissociated from the stomach of the toad Bufo marinus contract when stretched. Stretch-activated channels have been identified in these cells using patch-clamp techniques. In both cell-attached and excised inside-out patches, the probability of the channel being open (Po) increases when the membrane is stretched by applying negative pressure to the extracellular surface through the patch pipette. The increase in Po is mainly due to a decrease in closed time durations, but an increase in open time duration is also seen. The open-channel current-voltage relationship shows inward rectification and is not appreciably altered when K+ is substituted for Na+ as the charge-carrying cation in Ca2+-free (2 mM EGTA) pipette solutions bathing the extracellular surface of the patch. The inclusion of physiological concentrations of Ca2+ (1.8 mM) in pipette solutions (containing high concentrations of Na+ and low K+) significantly decreases the slope conductance as well as the unitary amplitude. The channel also conducts Ca2+, since inward currents were observed using pipette solutions in which Ca2+ ions were the only inorganic cations. When simulating normal physiological conditions, we find that substantial ionic current is conducted into the cell when the channel is open. These characteristics coupled with the high density of the stretch-activated channels point to a key role for them in the initiation of stretch-induced contraction.

Stretch‐induced enhancement of contractions in uterine smooth muscle of rats.

“…Kleinhaus & Kao (1969) (Nakayama & Tanaka, 1993 Ca2P channels (Kirber et at. 1988;Meininger & Davis, 1992).…”

“…SA channel activities were first reported by Guharay & Sachs (1984) in cultured embryonic chick skeletal muscle cells. Later, they were found in many other types of cells: oocytes and red blood cells (Yang & Sachs, 1987;, lens epithelial cells (Cooper, Tang, Rae & Eisenberg, 1986), hair cells (Ohmori, 1984;Hudspeth, 1985) and smooth muscle cells (Kirber, Walsh & Singer, 1988;Hisada, Ordway, Kirber, Singer & Walsh, 1991;Wellner & Isenberg, 1993). It has been shown that the inward currents flowing through SA channels tend to depolarize the cell.…”

Visualization of Ca2+entry through single stretch-activated cation channels

“…SACs were activated by applying negative pressure (suction) to the back end of the patch pipette as described previously (4,8). The single-channel unitary currents were recorded with an Axopatch-1D amplifier (Axon Instruments, Foster City, CA), using the cell-attached patch configuration of the patch-clamp technique.…”

“…[1][2][3]. SACs in smooth muscle have also been shown to be Ca 2ϩ permeable (4)(5)(6). This conclusion was obtained from patch-clamp ion substitution experiments where Ca 2ϩ was the only available carrier of the inward current.…”

“…Therefore, it has not been clearly demonstrated whether significant amounts of Ca 2ϩ can indeed enter the cell through SACs when physiological salt solutions are used, or whether the fraction of the current carried by Ca 2ϩ is large enough to have a significant effect on the intracellular [Ca 2ϩ ]. Nevertheless, SACs have been considered essential for stretch-induced contractions and vascular smooth muscle myogenic responses (4,(6)(7)(8). Two roles for SACs were proposed: to pass cations (mainly Na ϩ ) leading to membrane depolarization, and to pass Ca 2ϩ to increase the cytosolic [Ca 2ϩ ] either directly or indirectly by triggering Ca 2ϩ release from stores.…”