From classic electrophysiology to systems biology: the evolving role of the in situ rat hindlimb neuromuscular preparation
D. Zavodovskyi, N. Semenuk, O. Lehedza
- Bogomoletz Institute of Physiology of the NAS of Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz71.05.033

Abstract
The in situ rat hindlimb neuromuscular preparation serves as a pivotal experimental model in physiology
and biomedical research, enabling detailed investigations of skeletal muscle contractile function and neuromuscular transmission under conditions closely resembling the physiological state. This review article
systematically consolidates knowledge of this model, tracing its evolution from inception to its contemporary
multifaceted applications and directions for future development. The first section examines the historical
prerequisites that facilitated the development of this method, which established the foundations for understanding the electrical nature of nerve impulses and synaptic transmission. The second section is dedicated
to analyzing the contemporary utilization of this preparation in global scientific practice. It explores its
role in detail, encompassing the study of fundamental mechanisms of muscle contraction and fatigue, the
modeling of peripheral neuropathies, traumatic nerve and muscle injuries, and the investigation of muscle
dysfunction in systemic pathologies such as sepsis, diabetes mellitus, and spinal cord injury. Specific attention is given to the evolution of the methodology and its integration with modern electrophysiological
approaches. The third section analyzes the prospects for future applications of the model. Its designation as
a “gold standard” for the preclinical evaluation of novel therapeutic strategies is substantiated. New opportunities are discussed, including the integration of this model with nanotechnologies to study the impact
of nanoparticles on NO-dependent regulation of muscle contraction, as well as its integration with systems
biology technologies for a comprehensive analysis of neuromuscular function. The article emphasizes that,
despite its classical status, the in situ rat hindlimb neuromuscular preparation remains an indispensable and
relevant tool for addressing both fundamental and applied challenges in modern physiology and medicine.
Keywords: neuromuscular preparation, skeletal muscle, contractile force, rat, neuromuscular transmission,
muscle fatigue, electrophysiology, review.
Keywords:
neuromuscular preparation, skeletal muscle, contractile force, rat, neuromuscular transmission, muscle fatigue, electrophysiology, review
References
- Piccolino M. Animal electricity and the birth of electrophysiology: the legacy of Luigi Galvani. Brain Res Bull. 1998;46(5):381-407. doi:10.1016/S0361-9230(98)00026-4. PubMed
- Finkelstein G. Emil du Bois-Reymond: neuroscience, self, and society in nineteenth-century Germany. MIT Press; 2013. doi:10.7551/mitpress/9543.001.0001
- Bernard C. Leçons sur les effets des substances toxiques et médicamenteuses. Baillière; 1857. doi:10.5962/bhl.title.1834
- Gutmann E. The denervated muscle. Publishing House of the Czechoslovak Academy of Sciences; 1962. doi:10.1007/978-1-4899-4854-0
- Close R. Dynamic properties of mammalian skeletal muscles. Physiol Rev. 1972;52(1):129-197. doi:10.1152/physrev.1972.52.1.129. PubMed
- Burke RE, Levine DN, Tsairis P, Zajac FE 3rd. Physiological types and histochemical profiles in motor units of the cat gastrocnemius. J Physiol. 1973;234(3):723-748. doi:10.1113/jphysiol.1973.sp010369. PubMed PubMedCentral
- Ji LL, Yeo D. Mitochondrial dysregulation and muscle disuse atrophy. F1000Res. 2019;8:1621. doi:10.12688/f1000research.19139.1. PubMed PubMedCentral
- Rich MM, Pinter MJ. Crucial role of sodium channel fast inactivation in muscle fibre inexcitability in a rat model of critical illness myopathy. J Physiol. 2003;547(Pt 2):555-566. doi:10.1113/jphysiol.2002.035188. PubMed PubMedCentral
- Das A, Chakraborty A, Srivastav S, Kaur S, Jain S, Bade G. Study of neuromuscular transmission under fatigue, site of fatigue, and neuromuscular blocking in an in-situ rat nerve muscle preparation. Indian J Physiol Pharmacol. 2019;63(1):79-85.
- Fitts RH. Cellular mechanisms of muscle fatigue. Physiol Rev. 1994;74(1):49-94. doi:10.1152/physrev.1994.74.1.49. PubMed
- Allen DG, Lamb GD, Westerblad H. Skeletal muscle fatigue: cellular mechanisms. Physiol Rev. 2008;88(1):287-332. doi:10.1152/physrev.00015.2007. PubMed
- Angelidis A, Drzymała-Celichowska H, Kryściak K, Vandenboom R, Celichowski J. Concomitant effects of fatigue and potentiation in rat medial gastrocnemius fast motor units. Sci Rep. 2025;15(1):23085. doi:10.1038/s41598-025-07607-0. PubMed PubMedCentral
- Govbakh IO, Zavodovskiy DO, Bulgakova NV, Maznychenko AV, Vasylenko DA. Nerve conduction and neuromuscular transmission in C57Bl/6 mice with genetically determined peripheral neuropathy. Neurophysiology. 2019;51(4):248-252. doi:10.1007/s11062-019-09817-5
- Govbakh IO, Zavodovskiy DO, Bulgakova NV, Vasylenko DA, Maznychenko AV. Coordination of locomotor activity in transgenic C57Bl/6 mice with hereditary neuropathy. Neurophysiology. 2019;51(5):353-357. doi:10.1007/s11062-020-09829-6
- Juckett L, Saffari TM, Ormseth B, Senger JL, Moore AM. The effect of electrical stimulation on nerve regeneration following peripheral nerve injury. Biomolecules. 2022;12(12):1856. doi:10.3390/biom12121856. PubMed PubMedCentral
- Gordon T, Tyreman N, Raji MA. The basis for diminished functional recovery after delayed peripheral nerve repair. J Neurosci. 2011;31(14):5325-5334. doi:10.1523/JNEUROSCI.6156-10.2011. PubMed PubMedCentral
- Fletcher B, Phillips R, Faust A, Cook JL, Nuelle JAV. Physical exercise to promote regeneration after peripheral nerve injury in animal models: a systematic review. J Orthop Res. 2024;42(7):1608-1622. doi:10.1002/jor.25792. PubMed
- Zavodovskyi D. Study of traumatic injury to limb muscles in rats and mice: a narrative review. Neurophysiology. 2025. doi:10.1007/s11062-025-09960-2
- Zavodovskyi D, Lehedza O, Semenuk N, Kostyukov A. Mechanogram-based differentiation of post-amputation versus ischemic skeletal muscle dysfunction in rats. Neurophysiology. 2025. doi:10.1007/s11062-025-09966-w
- Frelichova V, Bém R, Chlupac J, Dubsky M. Animal experimental models of ischemic limbs: a systematic review. Vasc Pharmacol. 2023;153(2):107237. doi:10.1016/j.vph.2023.107237. PubMed
- Bonaldo P, Sandri M. Cellular and molecular mechanisms of muscle atrophy. Dis Model Mech. 2013;6(1):25-39. doi:10.1242/dmm.010389. PubMed PubMedCentral
- Zavodovskyi DO, Bulgakova NV, Sokolowska I, Piosik J, Maznychenko A. Water-soluble pristine C60 fullerenes attenuate isometric muscle force reduction in a rat acute inflammatory pain model. BMC Musculoskelet Disord. 2023;24:606. doi:10.1186/s12891-023-06719-w. PubMed PubMedCentral
- Callahan LA, Supinski GS. Sepsis-induced myopathy. Crit Care Med. 2009;37(10 Suppl):S354-S367. doi:10.1097/CCM.0b013e3181b6e439. PubMed PubMedCentral
- Lewis MT, Kasper JD, Bazil JN, et al. Skeletal muscle energetics are compromised only during high-intensity contractions in the Goto-Kakizaki rat model of type 2 diabetes. Am J Physiol Endocrinol Metab. 2019;317(3):E479-E490. doi:10.1152/ajpendo.00049.2019. PubMed PubMedCentral
- Zavodovskyi D, Lehedza O, Bulgakova N, Semenuk N, Kostyukov О. The method of evoked potentials as a promising direction for the study of nociception in anesthetized animals. Fiziol Zh. 2024;70(3):65-72. doi:10.15407/fz70.03.065
- Krause T, Gerbershagen MU, Fiege M, Weisshorn R, Wappler F. Dantrolene—a review of its pharmacology, therapeutic use and new developments. Anaesthesia. 2004;59(4):364-373. doi:10.1111/j.1365-2044.2004.03658.x. PubMed
- Reid MB. Role of nitric oxide in skeletal muscle: synthesis, distribution and functional importance. Acta Physiol Scand. 2001;172(4):245-255. doi:10.1046/j.1365-201X.2001.00880.x
- Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev. 2001;81(1):209-237. doi:10.1152/physrev.2001.81.1.209. PubMed
- Maréchal G, Gailly P. Effects of nitric oxide on the contraction of skeletal muscle. Cell Mol Life Sci. 1999;55(8-9):1088-1102. doi:10.1007/s000180050359. PubMed PubMedCentral
- Hernández A, Schiffer TA, Ivarsson N, et al. Dietary nitrate increases tetanic [Ca²⁺]i and contractile force in mouse fast-twitch muscle. J Physiol. 2012;590(15):3575-3583. doi:10.1113/jphysiol.2012.232777. PubMed PubMedCentral
- Shapoval LM, Dmytrenko OV, Sagach VF, Tsierkezos N, Ritter U. Systemic administrations of water-dispersible single-walled carbon nanotubes: activation of NOS in spontaneously hypertensive rats. Neurophysiology. 2020;52(2):101-109. doi:10.1007/s11062-020-09858-1
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