Smooth Muscle - Complete MBBS 1st Year Physiology Notes

1. Structure of Smooth Muscle Cells

• No striations - because thick (myosin) and thin (actin) filaments are present but NOT organized into sarcomeres. This is why smooth muscle looks "smooth" under light microscopy.
• Single, centrally placed nucleus
• Caveolae - small flask-shaped invaginations of the cell membrane that abut slightly developed sarcoplasmic tubules. These are the smooth muscle equivalent of the transverse tubule system in skeletal muscle. When an action potential enters the caveolae, it triggers Ca²⁺ release from the abutting sarcoplasmic reticulum.
• Sarcoplasmic reticulum - sparse and only slightly developed compared to skeletal muscle (see diagram below). Most Ca²⁺ therefore enters from the extracellular fluid rather than being released from intracellular stores.
• Dense bodies - scattered throughout the cytoplasm and attached to the cell membrane, equivalent to Z-lines in skeletal muscle. Actin filaments are anchored to these.
• Intermediate filaments (desmin) - form the cytoskeletal scaffolding that connects dense bodies.

2. Types of Smooth Muscle

Multi-Unit Smooth Muscle

• Composed of discrete, separate fibers, each operating independently
• Each fiber is often innervated by a single nerve ending, similar to skeletal muscle
• Outer surfaces are covered by a basement membrane-like substance (collagen + glycoprotein) that insulates fibers from each other
• Little or no gap junctions between cells - therefore no electrical coupling
• Each fiber acts as a separate motor unit
• Control is exerted mainly by nerve signals
• Examples: ciliary muscle of the eye, iris muscle, piloerector muscles of hair follicles, vas deferens

Unitary (Visceral / Syncytial) Smooth Muscle

• Hundreds to thousands of fibers arranged in sheets or bundles that contract together as a single unit ("unitary")
• Cell membranes are adherent at multiple points - force generated in one fiber transmits to the next
• Gap junctions connect adjacent cells - ions flow freely, so action potentials or depolarization currents spread from fiber to fiber
• This creates a functional syncytium (hence also called syncytial smooth muscle)
• Shows spontaneous pacemaker activity (slow waves) and can contract without direct nervous input
• Examples: walls of the gastrointestinal tract, bile ducts, ureters, uterus, urinary bladder, and many blood vessels

3. Membrane Potential and Action Potentials in Smooth Muscle

Resting Membrane Potential

Action Potentials in Unitary Smooth Muscle

• Typical fast action potentials, similar in shape to skeletal muscle spikes
• Duration: 10 to 50 milliseconds
• Can be triggered by: electrical stimulation, hormones, neurotransmitters, stretch, or spontaneous pacemaker activity

• The upstroke is similar to a spike potential, but repolarization is delayed for several hundred milliseconds to 1 second
• This prolonged plateau is responsible for the sustained contraction of some smooth muscle types
• Examples: uterus (especially during labour), certain vascular smooth muscle, ureter

Why Ca²⁺ Channels Dominate (Not Na⁺)

• Smooth muscle cell membrane has many voltage-gated Ca²⁺ channels but few voltage-gated Na⁺ channels
• Therefore, it is the inward flow of Ca²⁺ (not Na⁺) that is mainly responsible for the upstroke of the action potential
• Ca²⁺ channels open much more slowly than Na⁺ channels and remain open longer - this explains the prolonged plateau of certain smooth muscle action potentials
• Ca²⁺ entry performs a dual function: it both generates the action potential AND directly triggers contraction via the calmodulin pathway

4. Physiological Basis of Action Potentials in Unitary Smooth Muscle: Slow Wave Potentials

• Spontaneous, rhythmic oscillations of membrane potential that occur in unitary (visceral) smooth muscle
• They are not action potentials - they are not self-regenerative and do not spread like action potentials
• They are a local property of the smooth muscle fibers

1. Rhythmic waxing and waning of the Na⁺-K⁺ pump activity - when pump is active, more Na⁺ is expelled and the membrane hyperpolarizes; when pump slows, membrane depolarizes
2. Rhythmic changes in conductance of ion channels

• When the slow wave depolarizes the membrane from -60 mV to approximately -35 mV (the threshold for action potential generation in visceral smooth muscle), a full action potential fires
• This action potential spreads through the syncytium via gap junctions and triggers a coordinated contraction
• The slow waves set the frequency of contractions in hollow visceral organs (e.g., gastric slow waves: ~3/min; small intestine: ~12/min)
• Hence, slow waves are called pacemaker waves

5. Depolarization of Multi-Unit Smooth Muscle Without Action Potentials

• Nerve endings release neurotransmitters (ACh from parasympathetic fibers; norepinephrine from sympathetic fibers)
• These transmitters cause local depolarization of the cell membrane called the junctional potential
• Action potentials usually do NOT develop because:
  • The individual fibers are too small to generate a self-propagating action potential
  • In visceral smooth muscle, a critical mass of 30-40 fibers must depolarize simultaneously before a self-propagating action potential can be initiated. Multi-unit fibers, being individually small and isolated, cannot achieve this
• The junctional potential spreads electrotonically (passively, without regeneration) over the entire fiber
• This electrotonic spread is sufficient to cause contraction without requiring a full action potential
• This makes multi-unit smooth muscle contraction fine and graded, since each fiber responds individually and in proportion to the strength of neurotransmitter stimulation

6. Local Tissue Factors and Hormones Causing Contraction Without Action Potentials

Local Tissue Factors

Hormones

• Norepinephrine / epinephrine: Can cause contraction (via α₁-receptors, IP₃/DAG pathway raising intracellular Ca²⁺) or relaxation (via β₂-receptors, cAMP pathway)
• Acetylcholine: Contracts most visceral smooth muscle; relaxes some (via endothelium-derived NO in vessels)
• Oxytocin: Contracts uterine smooth muscle
• Angiotensin II: Contracts vascular smooth muscle
• Vasopressin (ADH): Contracts vascular smooth muscle
• Histamine: Contracts bronchial smooth muscle (causes bronchoconstriction in asthma)
• Serotonin (5-HT): Contracts GI smooth muscle
• Prostaglandins: Variable effects depending on type and receptor

• Hormone binds its receptor → activates Gq protein → activates phospholipase C → generates IP₃ + DAG
• IP₃ releases Ca²⁺ from sarcoplasmic reticulum (intracellular stores)
• This rise in intracellular Ca²⁺ activates the calmodulin-MLCK pathway (see Section 7) and causes contraction WITHOUT the membrane ever reaching action potential threshold

7. Regulation of Smooth Muscle Contraction by Calcium Ions

1. Ca²⁺ entry/release: Ca²⁺ enters from extracellular fluid via voltage-gated Ca²⁺ channels (opened during action potentials) AND is released from the sarcoplasmic reticulum (via IP₃ receptors or ryanodine receptors in response to hormones/neurotransmitters). The latent period for Ca²⁺ diffusion averages 200-300 ms (50x longer than skeletal muscle).
2. Calmodulin binding: The entering Ca²⁺ binds to calmodulin (CaM), a regulatory protein that is the functional analog of troponin C. Four Ca²⁺ ions bind per calmodulin molecule.
3. MLCK activation: The Ca²⁺-CaM complex activates myosin light chain kinase (MLCK), a phosphorylating enzyme.
4. Myosin phosphorylation: MLCK phosphorylates the regulatory light chain on each myosin head. When this light chain is NOT phosphorylated, the myosin head cannot interact with actin (cross-bridge cycling is impossible). When phosphorylated, the myosin head can bind to actin and undergo the full power-stroke cycle.
5. Cross-bridge cycling and contraction: The phosphorylated myosin heads repetitively attach to and detach from actin filaments, pulling them toward the center - shortening the cell and producing force. ADP and inorganic phosphate are released; ATP binds to allow detachment.
6. Relaxation: When intracellular Ca²⁺ falls, Ca²⁺ dissociates from calmodulin → MLCK becomes inactive → myosin light chain phosphatase (MLCP) dephosphorylates the regulatory light chain → cross-bridge cycling stops → the muscle relaxes.

• The sarcoplasmic reticulum is only slightly developed in smooth muscle
• Therefore, the majority of activating Ca²⁺ comes from extracellular fluid (extracellular [Ca²⁺] = >10⁻³ M; intracellular [Ca²⁺] = <10⁻⁷ M - a 10,000-fold gradient)
• Removing Ca²⁺ from extracellular fluid will abolish smooth muscle contraction much more readily than in skeletal muscle

8. The Latch Mechanism

What is the Latch Mechanism?

Physiological Basis

1. Initially, elevated Ca²⁺ → MLCK phosphorylates myosin → active cross-bridge cycling (high energy use, fast cycling)
2. As Ca²⁺ slowly falls, MLCP begins dephosphorylating the myosin light chains
3. However, some dephosphorylated (unlocked) myosin heads remain attached to actin without cycling - they become "latch bridges"
4. These latch bridges generate sustained tonic force but do NOT cycle repeatedly, so ATP consumption is dramatically reduced
5. The latch state is eventually released by further Ca²⁺ reduction or by specific signaling

Physiological Significance

• Allows hours of sustained tonic contraction at very low metabolic cost (e.g., blood vessel tone, sphincter tone, bronchial tone)
• A blood vessel can maintain arterial pressure all day with negligible ATP consumption compared to what would be required for continuous active cross-bridge cycling
• This explains why smooth muscle is the ideal muscle for organs requiring sustained tension maintenance

9. Stress Relaxation and Reverse Stress Relaxation

Stress Relaxation (Receptive Relaxation)

• The myosin cross-bridges and structural proteins of smooth muscle can slowly rearrange and "slip" to new positions at the new length
• The latch bridges gradually release and re-form in the new elongated configuration
• The muscle effectively "resets" its resting length to the new stretched length

• Allows the stomach, bladder, and uterus to accommodate large volumes at low pressure
• A full bladder does not generate very high wall pressure until it is ready to void, preventing inadvertent micturition
• The stomach can expand from ~50 mL (empty) to >1 L (full meal) without generating excessively high pressures that would cause pain or back-pressure on the esophagus

Reverse Stress Relaxation

• When muscle shortens, cross-bridges and structural elements rearrange to the shorter configuration
• MLCK activity and Ca²⁺ signaling maintain partial activation
• The muscle "resets" again to the new shorter length and generates appropriate wall tension

• Helps the bladder maintain detrusor tone and continue expelling urine even as it empties
• Helps the uterus maintain coordinated contractions during labour
• Allows hollow organs to maintain tone across a wide range of volumes, adapting their wall tension proportionally

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