The exchange of Ca++ between the extracellular fluid and myoplasm is facilitated by the sarcolemma. In smooth muscle, the sarcolemma contains numerous caveolae that play a role in regulating intracellular Ca++ and also serve as a scaffold for signaling molecules. The sarcoplasmic reticulum (SR) holds an intracellular pool of Ca++ that can be mobilized to temporarily increase the concentration of Ca++ in the myoplasm. The concentration of Ca++ in the myoplasm depends on the presence of extracellular Ca++. Transporters in the sarcolemma that regulate the concentration of Ca++ in the myoplasm include receptor-mediated Ca++ channels, voltage-gated Ca++ channels, Ca++-ATPase, and the 3Na+1Ca++ antiporter. The SR also has a role in regulating the concentration of Ca++ in the myoplasm. The Ca++ channels in the SR open in response to a chemical signal. Neurotransmitters or hormones that act through receptors in the sarcolemma can activate phospholipase C (PLC), which leads to the production of the second messenger inositol 1,4-triphosphate (InsP3). InsP3 then activates InsP3-gated Ca++ channels on the SR. Many agonists that activate PLC through G protein–coupled receptors also activate the RhoA/Rho kinase (ROK) signaling cascade, thereby increasing the sensitivity of smooth muscle contraction to Ca++. Smooth muscle SR also contains Ca++-gated Ca++ channels known as ryanodine receptors (RYR). Ca++ is reabsorbed into the SR through the sarcoplasmic endoplasmic reticulum Ca++ ATPase (SERCA).
Smooth muscles have contractile units that consist of small groups of thick myosin filaments that interlock with numerous thin filaments attached to dense bodies or membrane-dense areas equivalent to Z-lines. There are no striations present. Contraction occurs through a sliding filament–crossbridge mechanism.
Contraction of smooth muscle depends on both the release of Ca++ from the SR and the entry of Ca++ through the sarcolemma. Smooth muscle lacks troponin. Phosphorylation of cross-bridges by a Ca++-dependent myosin light chain kinase (MLCK) is necessary for attachment to the thin filament. Dephosphorylation of an attached cross-bridge by myosin phosphatase (MP) slows down its cycling rates. A higher concentration of Ca++ in the myoplasm increases the ratio of MLCK to MP activity, resulting in a greater number of phosphorylated cross-bridges throughout a cycle. This leads to higher shortening velocities.
The activity of smooth muscle is regulated by nerves (primarily autonomic), circulating hormones, locally generated signaling substances, connections with other smooth muscle cells, and even connections with other non–smooth muscle cells. Various hormones/agonists enhance the sensitivity of smooth muscle contraction to Ca++ by reducing the activity of MP and simultaneously increasing the activity of MLCK at a given intracellular concentration of Ca++. Activation of the RhoA/ROK signaling cascade contributes to the inhibition of MP and the stimulation of MLCK, thereby increasing the sensitivity of smooth muscle contraction to Ca++. Smooth muscle also has an inherent ability to respond to stretch, which is crucial for regulating blood flow to different tissues.
In response to sustained or tonic stimulation, smooth muscle undergoes a rapid contraction followed by sustained maintenance of force with reduced cross-bridge cycling rates and ATP consumption. This behavior, known as the latch state, is advantageous for muscles that need to withstand continuous external force, such as blood vessels that must endure blood pressure. During the latch state, ATP is consumed at a rate that is less than 1/300th of the rate required to maintain the same force in skeletal muscle.
The sarcolemma plays an important role in Ca++ exchange between extracellular fluid and myoplasm. The sarcolemma of smooth muscle contains numerous caveolae that contribute to regulation of intracellular [Ca++] and also appear to serve as a scaffold for signaling molecules. The sarcoplasmic reticulum (SR) contains an intracellular Ca++ pool that can be mobilized to transiently increase myoplasmic [Ca++]. Myoplasmic [Ca++] is dependent on extracellular Ca++ . Transporters in the sarcolemma that regulate myoplasmic [Ca++] include receptor-mediated Ca++ channels, voltage-gated Ca++ channels, Ca++-ATPase, and the 3Na+1Ca++ antiporter. The SR also regulates myoplasmic [Ca++]. The Ca++ channels in the SR open in response to a chemical. Neurotransmitters or hormones that act via receptors in the sarcolemma can activate phospholipase C (PLC), followed by generation of the second messenger inositol 1,4-triphosphate (InsP3). InsP3 then activates InsP3-gated Ca++ channels on the SR. Many agonists that activate PLC through G protein–coupled receptors also activate the RhoA/Rho kinase (ROK) signaling cascade, thereby increasing the sensitivity of smooth muscle contraction to Ca++ . Smooth muscle SR also contains Ca++-gated Ca++ channels (ryanodine receptor [RYR]). Ca++ reaccumulates in the SR via SERCA (sarcoplasmic endoplasmic reticulum Ca++ ATPase).
3.
Smooth muscles contain contractile units that consist of small groups of thick myosin filaments that interdigitate with large numbers of thin filaments attached to Z-line equivalents termed dense bodies or membrane-dense areas. No striations are evident. Contraction is caused by a sliding filament–crossbridge mechanism.
4.
Contraction of smooth muscle is dependent on both release of Ca++ from the SR and entry of Ca++ across the sarcolemma. Smooth muscle lacks troponin. Phosphorylation of cross-bridges by a Ca++-dependent myosin light chain kinase (MLCK) is necessary for attachment to the thin filament. Dephosphorylation of an attached cross-bridge by myosin phosphatase (MP) slows its cycling rates. Higher myoplasmic [Ca++] increases the ratio of MLCK to MP activity, with the result that more of the cross-bridges remain phosphorylated throughout a cycle. This increases shortening velocities.
5.
Smooth muscle activity is controlled by nerves (principally autonomic), circulating hormones, locally generated signaling substances, junctions with other smooth muscle cells, and even junctions with other non–smooth muscle cells. A variety of hormones/ agonists increase the sensitivity of smooth muscle contraction to Ca++ by reducing the activity of MP and reciprocally increasing the activity of MLCK at a given intracellular [Ca++]. Activation of the RhoA/ROK signaling cascade contributes to this inhibition of MP and stimulation of MLCK, and hence to the increase in sensitivity of smooth muscle contraction to Ca++ . Smooth muscle also has an intrinsic ability to respond to stretch, which is important for autoregulation of blood flow to various tissues.
6.
The response to sustained or tonic stimulation is a rapid contraction followed by sustained maintenance of force with reduced cross-bridge cycling rates and ATP consumption. This behavior, called the latch state, is advantageous for muscles that may need to withstand continuous external force, such as blood vessels, which must be able to withstand blood pressure. During the latch state, ATP is consumed at less than 1/300 the rate needed to maintain the same force in skeletal muscle.
7.