Notes:

https://mednotesbyrazaullah.blogspot.com/2026/08/chapter-8-excitation-and-contraction-of.html

Neurotransmitters at Smooth Muscle Junctions

Excitatory and Inhibitory Substances

Smooth muscle contraction is heavily regulated by chemical transmitter substances, with acetylcholine and norepinephrine acting as the primary agents. A critical concept emphasized by Guyton is that neither neurotransmitter is inherently excitatory or inhibitory. Instead, the response depends strictly on the specific receptor protein expressed on the muscle cell membrane. When a transmitter binds to an excitatory receptor, it depolarizes the membrane or opens ion channels to increase intracellular calcium, driving contraction. Conversely, binding to an inhibitory receptor causes hyperpolarization or closes calcium pathways, suppressing contraction. When acetylcholine excites a given smooth muscle tissue, norepinephrine inhibits it, and vice versa. Beyond autonomic nerves, Guyton notes that local tissue chemical factors such as oxygen deficiency, excess carbon dioxide, or decreased pH along with circulating hormones like epinephrine, vasopressin, and oxytocin, also act as powerful excitatory or inhibitory signals to fine-tune smooth muscle tone.

• Acetylcholine and norepinephrine are main autonomic transmitters.
• Same nerve fibers never secrete both transmitters.
• Acetylcholine excites smooth muscle in some organs.
• Acetylcholine inhibits smooth muscle in other organs.
• Norepinephrine usually opposes the action of acetylcholine.
• Transmitters bind to specific membrane receptor proteins.
• Receptors determine whether muscle is excited or inhibited.
• Receptors dictate which neurotransmitter causes the response.

Membrane Potentials in Smooth Muscle

Resting Membrane Potential

• Voltage depends on the momentary condition of the muscle.
• Normal resting potential is -50 to -60 mV.
• Resting potential is less negative than skeletal muscle.

Action Potentials in Unitary Smooth Muscle

• Action potentials occur in unitary smooth muscle.
• Multi-unit smooth muscle rarely displays action potentials.
• Occur as spike potentials or plateau potentials.

Spike Potentials

• Typical spike potentials occur in unitary muscle.
• Duration lasts 10 to 50 milliseconds.
• Triggered by electricity, hormones, transmitters, or stretch.
• Can generate spontaneously within muscle fibers.

Action Potentials with Plateaus

• Onset is similar to typical spike potentials.
• Repolarization is delayed up to 1000 milliseconds.
• Plateau accounts for prolonged muscle contractions.
• Occurs in ureter, uterus, and vascular muscle.

Role of Calcium Channels

• Membrane contains many voltage-gated calcium channels.
• Membrane contains few voltage-gated sodium channels.
• Sodium plays little role in action potentials.
• Calcium inflow mainly generates the action potential.
• Calcium channels open and close much slower.
• Slow channels cause prolonged plateau action potentials.
• Entering calcium directly activates the contractile mechanism.

Slow Wave Potentials and Spontaneous Action Potentials

• Some smooth muscle is self-excitatory without stimuli.
• Associated with basic slow wave rhythm of potential.
• Slow waves themselves are not action potentials.
• Slow waves are local properties of muscle.
• May result from varying sodium pump activity.
• May result from rhythmic ion channel conductance changes.
• Strong slow waves can initiate action potentials.
• Slow waves cannot directly cause muscle contraction.
• Potential rising to -35 mV triggers action potentials.
• Action potentials at wave peaks cause contractions.
• Slow waves act as pacemaker waves in 

Contraction Without Action Potentials

• About half of smooth muscle contraction lacks action potentials.
• Stimulating factors directly target the muscle contractile machinery.
• Non-nervous factors include local chemicals and various hormones.

Local Tissue Chemical Factors

• Smallest blood vessels have little or no nerve supply.
• Smooth muscle responds rapidly to local interstitial fluid changes.
• Resting small blood vessels normally remain contracted.
• Tissue blood flow increases when vessel walls relax.
• The local feedback system controls local area blood flow.
• Oxygen lack causes smooth muscle relaxation and vasodilation.
• Excess carbon dioxide causes local vasodilation.
• Increased hydrogen ion concentration causes local vasodilation.
• Adenosine and lactic acid induce local vasodilation.
• Increased potassium ions cause local vasodilation.
• Diminished calcium ions cause local vasodilation.
• Increased body temperature causes local vasodilation.

Effects of Hormones

• Circulating blood hormones affect smooth muscle contraction.
• Key hormones include epinephrine, norepinephrine, and acetylcholine.
• Angiotensin, endothelin, vasopressin, and oxytocin affect contraction.
• Serotonin and histamine also influence smooth muscle contraction.
• Excitatory hormone receptors trigger smooth muscle contraction.
• Inhibitory hormone receptors cause smooth muscle relaxation.

Mechanisms of Action

• Hormone receptors can open sodium or calcium channels.
• Membrane depolarization can initiate or enhance action potentials.
• Depolarization without action potentials allows calcium entry.
• Inhibition occurs when sodium and calcium channels close.
• Opening potassium channels allows positive ions to exit.
• Increased intracellular negativity causes cell hyperpolarization.
• Hyperpolarization strongly inhibits smooth muscle contraction.
• Hormones can act without changing membrane potential.
• Receptor activation can trigger internal sarcoplasmic calcium release.
• Receptors can activate adenylate or guanylate cyclase enzymes.
• Enzyme activation forms cAMP or cGMP second messengers.
• Second messengers alter enzyme phosphorylation to inhibit contraction.
• Calcium pumps move calcium into the reticulum or extracellularly.
• Decreased intracellular calcium concentration causes muscle relaxation.
• The same substance can cause opposite effects in different locations.
• Norepinephrine inhibits gut muscle but contracts vascular muscle.

Sources of Calcium Ions for Contraction

Extracellular Fluid vs. Sarcoplasmic Reticulum

• Calcium ions activate smooth muscle contractile processes.
• Sarcoplasmic reticulum is poorly developed in smooth muscle.
• Most calcium enters from the extracellular fluid.
• Extracellular calcium concentration is higher than intracellular.
• Open calcium channels cause rapid inward calcium diffusion.
• Calcium diffusion requires 200 to 300 milliseconds.
• Latent period is 50 times longer than skeletal.

Role of Caveolae and Sarcoplasmic Reticulum

• Sarcoplasmic tubules lie near the cell membrane.
• Membrane invaginations called caveolae about sarcoplasmic tubules.
• Caveolae serve as rudimentary analogs to T tubules.
• Action potentials in caveolae trigger sarcoplasmic calcium release.
• More extensive sarcoplasmic reticulum leads to faster contraction.

Extracellular Calcium Dependency

• Smooth muscle contraction depends heavily on extracellular calcium.
• Dropping extracellular calcium to 1/3 or 1/10 stops contraction.

Calcium Removal and Relaxation

• Smooth muscle relaxation requires intracellular calcium removal.
• Calcium pumps transport calcium outward or into the reticulum.
• Smooth muscle calcium pump is slow-acting.
• Single contraction lasts for seconds instead of milliseconds.