Recently, it has been shown that transient receptor potential melastatin 7 (TRPM7) expression is modified by vasoactive agents (aldosterone and angiotensin II), suggesting a potential role for TRPM7 in hypertension. TRPM7 is a ubiquitously expressed chanzyme (channel + enzyme) that contains a cation permeable pore, as well as a kinase domain at the COOH-terminus. It is also essential for life, as genetic deletion of TRPM7 in mice is embryonic lethal. At pH 7.4 and with Mg2+ in solution, TRPM7 exhibits non-rectifying inward kinetics, rectifying outward kinetics, and a reversal potential of 0 mV. Under these conditions, TRPM7 is permeant to divalent cations at negative potentials and monovalent cations at positive potentials. Presently, it is not known if the vasoactive agents mentioned above alter TRPM7s functional characteristics. Thus, the purpose of this study was to determine the effects of aldosterone on TRPM7s biophysical properties in tetracycline-induced, stably-expressed HEK293 cells. Using whole-cell voltage-clamp, currents where characterized using a ramp protocol from -100 mV to +100 mV (50 ms), at a frequency of 0.5 Hz. Current-voltage (IV) relationships were statistically compared between aldosterone treated and control cells using repeated measures two-way ANOVAs with post bonferroni tests. Currents (pA) are expressed as mean ± S.E.M. The results indicate that TRPM7 is functionally modulated by 100 nM aldosterone, only after 18 hour (h) induction (control, n=7; aldosterone, n=8; P = 0.0099). Direct application of aldosterone using superfusion (0 h; n = 6), or after a 4 h induction period (n = 5), generated superimposed IV relationships compared to controls (n = 8). As well, the aldosterone effect at 18 h is only seen in the rectifying component of the IV relationship, becoming significant at 80 mV. At this voltage, current values for control, time 0 h, time 4 h, and time 18 h aldosterone were 2204.3 ± 226.8 pA (n = 8), 2247.6 ± 182.0 pA (n = 6), 2304.2 ± 249.9 pA (n = 5), and 3172.2 ± 104.3 pA (P < 0.0001, n = 6), respectively. Also, both control (+80mV, 1680.1 ± 109.8; n = 7) and 18 h aldosterone stimulated currents (+80mV, 2827.0 ± 341.4; n = 8) were blocked by application of 50 µM 2-aminoethoxydiphenyl bromate (control: 601.6 ± 139.6, n = 6; 18 h aldosterone: 669.0 ± 204.9, n = 4), a known TRPM7 blocker. Finally, when comparing western blot analysis of control and 18 h induced aldosterone cell lysates (n = 1), there was no effect on the amount of TRPM7 or mineralocorticoid receptor protein. Thus, aldosterone has a very specific biophysical effect on TRPM7 ion channels, requires over 4 hours of induction time to do so and is not dependent on cellular TRPM7 protein levels. These results suggest that aldosterone is transcriptionally activating a regulatory factor that modulates TRPM7. The connection between this modulation and hypertension remains to be determined.