Decreased Extracellular Calcium Increases Skeletal Muscle Excitability Without Directly Affecting Contractile Force
Decreased extracellular calcium increases skeletal muscle fiber excitability by altering membrane ion channel properties and reducing the threshold for action potential generation, while contractile force remains unaffected because skeletal muscle contraction depends entirely on intracellular calcium released from the sarcoplasmic reticulum, not extracellular calcium influx.
Mechanism of Increased Excitability with Low Extracellular Calcium
Effect on Membrane Excitability
Membrane excitability depends on ion gradients across the membrane and properties of ion gating channels, which are influenced by the chemical milieu, especially Ca2+ concentrations 1.
Low extracellular calcium reduces the stabilizing effect of calcium on the sarcolemma, making voltage-gated sodium channels more readily activated 1.
The active components of membrane excitability (ion channel gating) are directly influenced by extracellular Ca2+ concentrations, affecting the threshold voltage required to generate action potentials 1.
This increased excitability manifests as a lower rheobase current needed to trigger action potentials and enhanced propagation of electrical signals along muscle fiber membranes 2.
Calcium's Role as a Membrane Stabilizer
Extracellular calcium ions bind to negatively charged sites on the external surface of the cell membrane, effectively screening surface charges and stabilizing the membrane potential 1.
When extracellular calcium is reduced, this screening effect diminishes, making the membrane more electrically unstable and easier to depolarize 3.
The voltage sensor of excitation-contraction coupling in the T-tubular membrane is directly affected by extracellular calcium, with low [Ca2+]o causing a left shift (29 mV) in the inactivation curve of calcium release 3.
Why Contractile Force Remains Unaffected
Independence from Extracellular Calcium
Skeletal muscle fibers can produce normal twitches for many minutes when external Ca2+ is lowered to 10^-8 M with EGTA, demonstrating that extracellular calcium is not required for contraction 4.
The slow inward calcium current (ICa) through the sarcolemma has no obvious role in muscle excitation-contraction coupling in skeletal muscle 4.
When ICa was decreased or eliminated with the calcium-blocking agent diltiazem, the same concentration that blocked calcium influx actually potentiated twitch, tetanic, and contracture tensions 4.
Dependence on Sarcoplasmic Reticulum Calcium
Skeletal muscle contraction is triggered by calcium released from the sarcoplasmic reticulum (SR) into the myoplasm in response to membrane depolarization, not by extracellular calcium entry 5, 3.
During excitation-contraction coupling, Ca2+ released from the SR diffuses to the thin filaments where it binds to troponin regulatory sites to activate muscle contraction 5.
The SR contains sufficient calcium stores to support multiple contractions without requiring extracellular calcium influx 4, 5.
The T-tubular system is responsible for rapid inward spread of excitation and signal transfer to the SR to release Ca2+, but this process does not require extracellular calcium entry 6.
Clinical and Physiological Context
Distinction from Cardiac Muscle
This phenomenon is specific to skeletal muscle and differs fundamentally from cardiac muscle, where extracellular calcium influx through L-type calcium channels is essential for triggering SR calcium release (calcium-induced calcium release) 1.
In cardiac muscle, the major pathway for Ca2+ influx is through L-type Ca2+ channels, and reduction in extracellular calcium directly impairs contractility 1.
Practical Implications
The increased excitability with low extracellular calcium can manifest as muscle hyperexcitability, tetany, or spontaneous contractions in hypocalcemic states 1.
Despite increased excitability, the force-generating capacity of skeletal muscle remains intact as long as SR calcium stores are adequate 4, 5.
The threshold for action potential generation decreases, but once triggered, the action potential propagates normally through the T-tubular system to release SR calcium 6, 3.