Acetylcholine (ACh) activates the inwardly rectifying muscarinic K+ channel in rat atrial cells via pertussis toxin (PTX)-sensitive G-protein (Gk) coupled with the muscarinic receptor (mAChR). Although this K+ (KACh) channel function has reported to be modulated by the phosphorylation process, a kinase and phosphatase involved in these processes are still unclear. Since either PKA or PKC was not effective on this ATP-modulation, the present study examined the possible involvement of the protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) in the function of the KACh Channel. In the inside-out (I/O) patch preparation excised from the adult rat atrial cell, when activated by 10 μM ACh in the pipette and 100 μM GTP in the bath, the mean open time (τo) and the channel activity (KACh) was 1.13 ms (n=5) and 0.19 (n=6), respectively. Following the application of 1 mM ATP into the bath, τo increased by 34% (1.54 ms, n=5) and KACh by 66% (0.28, n=6). Channel function elevated by ATP was lasted after washout of ATP. However, this ATP-induced increase in the KACh channel function did not occur in pretreated cells with genistein (50 ~ 100 μM), a selective PTK inhibitor, but occurred in pretreated cells with equimolar daidzein, a negative control of the genistein. On the contrary, PTP which acts on tyrosine residue conversely reversed both ATP-induced increased τo by 32% (1.20 ms, n=3) and KACh by 41% (0.15, n=3), respectively. Taken together, these results suggest that KACh channel may, at least partly, be regulated by the tyrosyl phosphorylation, although it is unclear where this process exerts on the muscarinic signal transduction pathway comprising the mAChR-Gk-the KACh channel.