Transient receptor potential melastatin member 4 (TRPM4) encodes a Ca+ activated non-selective cation channel and functionally expressed in several tissues including the heart. Pathogenic mutants in TRPM4 gene have been reported in patients with inherited cardiac diseases including conduction blocks and Brugada syndrome. Heterologous expression of mutant channels in cell lines indicates that these mutations can lead to either increase or decrease in the expression and function of TRPM4 at the cell surface. While the expression studies and clinical variant studies further complement the importance of TRPM4 in cardiac function, electrophysiological characterization of cardiac phenotype in TRPM4 knockdown mice model can reveal more consolidated role of the ion channel in situ. In this study we performed patch clamp studies on isolated atrial and ventricular cardiac myocytes from male C57BL/6N mice, Wild type (WT) or TRPM4 knockdown (TRPM4-/-). Action potentials (AP) were measured in current clamp using perforated patch-clamp configuration and data were presented as mean ± SEM (N – number of mice, n – number of cells studied).There significance were studied using student t-test. In ventricular myocytes we observed a decrease in the AP upstroke velocity of TRPM4-/- mice (115.75 ± 3.7 V/s (WT) vs 89.7 ± 3.7 V/s (TRPM4-/-), N=5, n=14). The decrease in the upstroke velocity in TRPM4-/- mice was concomitant to a decrease in whole cell peak sodium current density by ~ 27% (-36.0 ± 4.4 pA/pF vs -26.1 ± 1.8 pA/pF, N = 5;n=10). AP recordings from atrial myocytes did not show any change in the upstroke velocity (108.0 ± 15.5 V/s vs 107.0 ± 15.1 V/s, N=5;n=23).However, the peak sodium current density was significantly reduced in these cells by ∼ 25% in TRPM4-/- (-48.0 ± 2.3 pA/pF vs -36.3 ± 2.5 pA/pF, N = 5; n=20). We further explored the effect of decrease in sodium current in cardiac myocytes recording pseudo electrocardiogram (ECGs) on explanted Langendorff perfused mice heart. Under basal condition, the (ECGs) did not show any change, however introducing mexiletine (40 µg/ml) a sodium channel inhibitor in the perfusate broadened the QRS by 18 ms (11.8 ± 1.8 ms (buffer) vs 29.1 ± 3.6 ms (mexiletine) N =5) in WT hearts. The effect of mexiletine was much more prominent in TRPM4-/- with a broadening of QRS complex by 41 ms (10.3 ± 0.9 ms (buffer) vs 51.1 ± 10.3 ms (mexiletine) N=5). The increased sensitivity of TRPM4-/- mice ECGs towards mexiletine, further complement our observation of decreased peak sodium current in ventricular myocytes. Our study gives the first evidence of TRPM4 expression directly impacting sodium current in mice cardiac myocytes. Future studies on patient derived cardiac iPSc (induced pluripotent stem cell) harboring TRPM4 loss-of-function variants and evaluating the impact on sodium current will be critical for developing novel therapeutic management in such patients.