Physiology of Smooth Muscle

Now we're onto the second topic for PHYL3001! (I already feel like I've forgotten everything about electrophysiology...)

Identify the characteristics that distinguish smooth muscle from cardiac and skeletal.

See previous post: Tissues
tl;dr: Smooth muscle is smooth. OMG

Oh wait, there is something else that I need to tell you. The following is apparently a tl;dr version of PHYL2002, which I didn't do. Contractions in all kinds of muscles ultimately result from Ca²⁺ binding to something, but that something is different in smooth muscle compared to the other two types of muscles. In cardiac and skeletal muscle, Ca²⁺ binds to troponin on the actin filament, whereas in smooth muscle, Ca²⁺ binds to calmodulin. This results in a Ca²⁺-calmodulin complex, which can activate myosin light chain kinase (MLCK). MLCK can phosphorylate the light chains in smooth muscle, activating ATPases and causing contraction of smooth muscle.

Define single and multi unit smooth muscle, tonic and phasic contraction for smooth muscle.

Tonic and phasic contractions

Tonic contractions are not rhythmic, whereas phasic contractions are. w00t w00t.

Single-unit smooth muscle

Single-unit smooth muscle all contracts as a single unit due to the presence of gap junctions between the cells (sorta like heart muscle). Some, such as the bladder and small blood vessels, can undergo tonic contractions, whereas others, such as the gut and uterus, can undergo phasic contractions. They often show something called "slow waves" or "basal electrical rhythm," which I will talk about in a bit.

Multi-unit smooth muscle

Multi-unit smooth muscle has discrete motor units that have to be activated separately, like skeletal muscle. These muscles only show tonic contraction. Examples of multi-unit smooth muscle include those in the eye, large blood vessels and airways.

List the receptors activated by the neurotransmitters ACh, NA/Adr, NO and ATP.

• ACh- Muscarinic cholinergic receptors. Causes contraction.
• NA/Adr- Can bind to α-adrenergic receptors to cause contraction, or β-adrenergic receptors to cause relaxation.
• NO- Can bind to guanylyl cyclase to cause relaxation.
• ATP- Can bind to P_2X receptors to cause contraction.

Explain the spontaneous contractions of gut, including the role of gap junctions, ICC, slow waves and action potentials.

As mentioned above, single-unit smooth muscle has gap junctions, making it easier for an action potential in one cell to propagate through to others. I also mentioned the basal electrical activity of this type of smooth muscle. But what sets all this off in the first place?

To my understanding, this is caused by ICCs, or Interstitial Cells of Cajal. They essentially act as the paceemaker cells of the gut. ICCs are located in the mucosa and submucosal plexuses, and are connected to smooth muscle cells via gap junctions. It is these cells that cause the "slow waves" of spontaneous, transient inward currents that are largely carried by Ca²⁺.

Slow waves do not cause contractions on their own. They can, however, cause action potentials if they depolarise the cell past the threshold potential. If the threshold is exceeded for long enough, many action potentials will result, which is good, because in smooth muscle many action potentials are required in order to cause a contraction. Neurotransmitters such as ACh can increase the strength of contraction by depolarising the cell to a larger extent, resulting in the cell spending more time above threshold and thus generating more action potentials. (Adrenaline does the opposite.)

Describe the channels and ions involved in smooth muscle action potentials and the actions of nifedipine/verapamil.

At rest, K_ir (inward rectifying) channels are open as they aren't being blocked by Mg²⁺ (see this post for more information). This allows potassium to move in the direction of its concentration gradient, which happens to be out of the cell.

When the cell depolarises, K_ir channels close. As mentioned in this post, these channels close, rather than open, when the cell becomes depolarised. At the same time, Ca²⁺ channels open, increasing Ca²⁺ inside the cell. As mentioned earlier, this allows Ca²⁺ to bind to calmodulin, activating MLCK and thus causing contraction.

Repolarisation occurs when K_v channels open. (You may also see them denoted as K_dr- delayed rectifier- channels.) This allows K⁺ to rush out and the cell to return to its resting potential.

Explain how some smooth muscle do not show action potentials including the relevant ion channels and ion movements.

Yeah, that's right, not all smooth muscles have action potentials. Airway smooth muscle, vascular muscle and others do not show action potentials, even when electrically stimulated. So I guess we'll all just have to throw out our ideas of "action potential = contraction." Damn.

A lack of action potentials is characteristic of many tonic smooth muscles. They can show graded depolarisations, but not full-on action potentials. This is because their K_v channels open really early- in fact, they open pretty much as soon as the cell depolarises. (There's a shit-ton of different K_v channels, so of course some of them have to be different >_>.) Additionally, these cells have K_Ca channels, or calcium-activated K⁺ channels, which I mentioned here but didn't discuss in any detail whatsoever. As their name suggests, they are K⁺ channels that open in response to an increase in Ca²⁺. Therefore, when depolarisation causes Ca²⁺ to come in, these K_Ca channels also open, increasing efflux of K⁺. All of this prevents the membrane potential from "spiking."