Objective: We have recently shown that the cation channel TRPV4 is functionally expressed in mouse skeletal muscle. TRPV4 activation can modulate background Ca2+ influx and muscle fatigue. TRPV4 deficient mice show, however, no muscle related phenotype. To further investigate the role of TRPV channels in skeletal muscle, we studied gene expression and background Ca2+ influx in skeletal muscle of normal and TRPV4-/- mice. Methods: RNA was isolated from mouse skeletal muscles (M. tibialis anterior (TA), M. extensor digitorum longus (EDL) and M. soleus (SOL). The Taqman RT- PCR technique was applied to quantify the expression of 25 TRP channel genes. The mRNA levels of TRP ion channels are given relation to that of 18S rRNA. The background Ca2+ influx, characteristic for muscle fibres was estimated with the manganese quench technique and Fura-2. Results: Gene expression of TRP channels was largely identical in muscles of wildtype and TRPV4-/- mice. However, TRPV4 and TRPV2 expression were clearly higher in the slow twitch soleus muscle compared to the fast twitch EDL. Relative mRNA levels for wildtype SOL were on average 0.15 (V2) and 0.017 (V4), while for EDL they yielded only 0.033 (V2) and 0.0005 (V4), respectively (n = 8). Furthermore, in muscles of TRPV4-/- mice, in particular in soleus muscle, we found an increased expression of TRPV2 (wildtype: 0.08, knockout: 0.14, n=8). The background influx of divalent cations in TRPV4-/- fibres was not different from controls. The quench of Fura-2 was on average 3.84 % per min (wildtype) and 3.99 % per min for fibres from TRPV4-/- mice. Conclusion: Our results show that TRPV2 and TRPV4 are expressed at different levels in fast and slow twitch muscle. In muscles of TRPV4-/- mice TRPV2 gene expression is upregulated. The background Ca²⁺ influx that is attributed to the activity of TRP channels, is unchanged in muscle fibres of TRPV4-/- mice. The latter effect may be explained by a compensatory upregulation on TRPV2.