The muscle contraction continues until the sarcoplasmic reticulum (SR) pumps calcium ions (Ca++) back in and the intracellular Ca++ levels decrease. As the Ca++ levels decrease, it dissociates from troponin C, causing the troponin-tropomyosin complex to move and block the myosin binding sites on the actin filament. If there is a depletion of ATP, as seen in cases of death, the cycle stops, resulting in abnormal muscle function. Brody's disease, a rare condition affecting 1 in 10,000,000 births, can be either autosomal recessive or autosomal dominant and may involve mutations in up to three genes. It is believed to result from decreased activity of the SERCA1 Ca++ pump found in fast-twitch skeletal muscle. Decreased SERCA1 activity has been linked to mutations in the gene encoding SERCA1, although another factor may contribute to the decreased SR Ca++ uptake in individuals with Brody's disease.

Myotonia congenita is also characterized by prolonged muscle contractions, specifically painless cramping, following voluntary contractions. This condition is caused by mutations in the CLCN1 gene, which encodes the chloride voltage-gated channel 1 in the sarcolemma and T-tubules of skeletal muscles. Chloride conductance in skeletal muscle plays a vital role in repolarization and stabilization of the membrane potential. Reduced chloride conductance in individuals with myotonia congenita leads to hyperexcitability of the muscle fiber, resulting in prolonged contractions and cramping after voluntary contractions. Epinephrine, particularly during stressful situations, often exacerbates the condition. Muscle stiffness can be relieved by repeated contractions, known as the warm-up phenomenon, although the underlying mechanism is not fully understood. Mutations in the CLCN1 gene in myotonia congenita can be transmitted in either an autosomal recessive manner (as in Becker's disease) or an autosomal dominant manner (as in Thomsen's disease). The worldwide prevalence of myotonia congenita is approximately 1 per 100,000, with a higher incidence (around 1 in 10,000) in northern Scandinavia.

In the rigor mortis state, muscle rigidity occurs due to the formation of permanent actin-myosin complexes. The thick filaments are formed by the association of myosin molecules in a tail-to-tail configuration, creating a bipolar orientation that allows myosin to pull the actin filaments towards the center of the sarcomere during the cross-bridge cycle. The myosin molecules are helically arranged in the thick filament, with cross-bridges extending towards each of the six thin filaments surrounding the thick filament.
If intracellular [Ca++] is still elevated, myosin undergoes another cross-bridge cycle and produces further contraction of the muscle. The ratchet action of the cross-bridge is capable of moving the thin filament approximately 10 nm. The cycle continues until the SERCA pumps Ca++ back into the SR. As [Ca++] falls, Ca++ dissociates from troponin C, and the troponin-tropomyosin complex moves and blocks the myosin binding sites on the actin filament. If the supply of ATP is exhausted, as occurs with death, the cycle stops abnormalityisseeninmusclesofthelegs,arms,andeyelid,andtheresponseisworsenedincoldweather.Brody’sdiseasecanbeeitherautosomalrecessiveorautosomaldominantandmayinvolvemutationsinuptothreegenes;however,itisrare(affecting1per10,000,000births).ItappearstoresultfromdecreasedactivityoftheSERCA1Ca++ pumpfoundinfast-twitchskeletalmuscle(seethesection ”).ThedecreasedactivityofSERCA1hasbeenassociatedwithmutationsinthegenethatencodesSERCA1,althoughanotheraccessoryfactormaycontributetothedecreasedSRCa++ uptakeinthefast-twitchskeletalmuscleofindividualswithBrody’sdisease.
Myotoniacongenitaisalsoassociatedwithprolongedmusclecontractions(painlesscramping)aftervoluntarycontractions,asaresultofmutationsintheCLCN1 gene,whichencodesthechloridevoltage-gatedchannel1inskeletalmusclesarcolemmaandTtubules.Chlorideconductanceintheskeletalmuscleisimportantforrepolarizationandstabilizationofthemembranepotential,andsothereducedchlorideconductanceinskeletalmusclesofindividualswithmyotoniacongenitaresultsinhyperexcitabilityofthemusclefiber.Voluntarycontractionmaythereforebefollowedbyaseriesofactionpotentials(afterdepolarizations)inthemusclethatresultinprolongedcontractions(i.e.,cramping).Epinephrine(e.g.,duringstressfulsituations)oftenworsensthecondition,asshowninmyotonic(“fainting”)goats.Musclestiffnesscanberelievedbyrepeatedcontractions(i.e.,thewarm-upphenomenon),althoughthemechanismunderlyingthewarm-upphenomenonisnotknown.MutationsintheCLCN1 geneinmyotoniacongenitamaybetransmittedineitheranautosomalrecessivemanner(asinBecker’sdisease,onetypeofmyotoniacongenita)oranautosomaldominantmanner(asinThomsen’sdisease,theothertypeofmyotoniacongenita).Theprevalenceofmyotoniacongenitaisapproximately1per100,000worldwide;theincidenceishigher(≈1:10,000)innorthernScandinavia.
in state c with the formation of permanent actin-myosin complexes (i.e., the rigor state). In this state, the muscle is rigid, and the condition is termed rigor mortis.
As already noted, formation of the thick filaments involves the association of myosin molecules in a tail-totail configuration to produce a bipolar orientation (see
Fig. 12.6 ). Such a bipolar orientation allows myosin to pull the actin filaments toward the center of the sarcomere during the cross-bridge cycle. The myosin molecules are also oriented in a helical array in the thick filament in such a way that cross-bridges extend toward each of the six thin filaments surrounding the thick filament (see
Fig.