The classic type of transient receptor potential channel (TRPC) is a molecular candidate for Ca2+-permeable cation channel in mammalian cells. TRPC5 is rapidly desensitized after activation by G protein-coupled receptor. Herein we report the effect of dimethyl sulfoxide (DMSO) on the desensitization of TRPC5. TRPC5 was initially activated by muscarinic stimulation with 50μM carbachol (CCh) and then decayed rapidly even in the presence of CCh (desensitization). DMSO in the pipette solution slowed the rate of this desensitization. Under the control conditions, TRPC5 current spontaneously declined to 6±1% of the initial peak amplitude 60 sec after CCh application and to 1±0.5% after 120 sec. But, in the presence of 0.01%, 0.1% and 1% DMSO, TRPC5 current spontaneously declined to 55±2%, 68±1% and 100±0.2% of the initial peak amplitude 60 sec after CCh application and to 38±2%, 61±1% and 100±1% after 120 sec, respectively. The results suggest that DMSO can internally attenuate the desensitization of TRPC5 current through unknown mechanisms that remain to be elucidated.