["\nAbstract\n\nAim\nLoading‐induced tension development is often assumed to constitute an independent cue to initiate muscle protein synthesis following resistance exercise. However, with traditional physiological models of resistance exercise, changes in loading‐induced tension development also reflect changes in neural activation patterns, and direct evidence for a mechanosensitive mechanism is therefore limited. Here, we sought to examine the importance of excitation and tension development per se on initiation of signalling, gene transcription and protein synthesis in rat skeletal muscle.\n\n\nMethods\nIsolated rat extensor digitorum longus muscles were allocated to the following interventions: (a) Excitation‐induced eccentric contractions (ECC); (b) Passive stretching without excitation (PAS); (c) Excitation with inhibition of contractions (STIM + IMA) and; (d) Excitation in combination with both inhibition of contractions and PAS (STIM + IMA + PAS). Assessment of transcriptional and translational signalling, gene transcription and acute muscle protein synthesis was compared in stimulated vs contra‐lateral non‐stimulated control muscle.\n\n\nResults\nProtein synthesis increased solely in muscles subjected to a combination of excitation and tension development (ECC and STIM + IMA + PAS). The same pattern was true for p38 mitogen‐activated protein kinase signalling for gene transcription as well as for gene transcription of immediate early genes FOS and JUN. In contrast, mechanistic target of rapamycin Complex 1 signalling for translation initiation increased in all muscles subjected to increased tension development (ECC and STIM + IMA + PAS as well as PAS).\n\n\nConclusions\nThe current study suggests that exercise‐induced increases in protein synthesis as well as transcriptional signalling is dependent on the concomitant effect of excitation and tension development, whereas signalling for translation initiation is only dependent of tension development per se.\n\n", "Acta Physiologica, Volume 231, Issue 1, January 2021. "]