The investigation of the TRPM genes and proteins in human cells is an area of intense recent study and, at times, debate.
Montell et al. (
2002) have reviewed the research into the TRP genes, and a second review by Montell (2003) has reviewed the research into the TRPM genes.

The TRPM family of ion channels has members throughout the metazoa.
The TRPM6 and TRPM7 proteins are highly unusual, containing both an ion channel domain and a kinase domain (Figure 1.7), the role of which brings about the most heated debate.

The activity of these two proteins has been very difficult to quantify.
TRPM7 by itself appears to be a Ca²⁺ channel but in the presence of TRPM6 the affinity series of transported cations places Mg²⁺ above Ca²⁺. The differences in reported conductance were caused by the expression patterns of these genes.
TRPM7 is expressed in all cell types tested so far, while TRPM6 shows a more restricted pattern of expression.
An unfortunate choice of experimental system by Voets et al., (
2004) led to the conclusion that TRPM6 is a functional Mg²⁺ transporter.
However, later work by Chubanov et al. (
2004) clearly showed that TRPM7 is required for TRPM6 activity and that the results of Voets et al.
are explained by the expression of TRPM7 in the experimental cell line used by Voets et al.
in their experiments.
Whether TRPM6 is functional by itself is yet to be determined.

The predicted TM topology of the TPRM6 and TRPM7 proteins has been adapted from Nadler et al. (
2001), Runnels et al. (
2001) and Montell et al. (
2002), this figure shows the computer predicted membrane topology of the TRPM6 and TRPM7 proteins in Homo sapiens.
At this time, the topology shown should be considered a tentative hypothesis.
The TM domains are shown in light blue, the pore loop in purple, the TRP motif in red and the kinase domain in green.
The orientation in the membrane and the positions of the N- and C-termini are indicated and the figure is not drawn to scale.

The conclusions of the Voets et al. (
2004) paper are probably incorrect in attributing the Mg²⁺ dependent currents to TRPM7 alone, and their kinetic data are likely to reflect the combined TRPM7/ TRPM6 channel.
The report presents a robust collection of data consistent with a channel-like activity passing Mg²⁺, based on both electrophysiological techniques and also mag-fura 2 to determine changes in cytoplasmic free Mg²⁺.
The investigation of the TRPM genes and proteins in human cells is an area of intense recent study and, at times, debate. Montell et al. (2002) have reviewed the research into the TRP genes, and a second review by Montell (2003) has reviewed the research into the TRPM genes.
The TRPM family of ion channels has members throughout the metazoa. The TRPM6 and TRPM7 proteins are highly unusual, containing both an ion channel domain and a kinase domain (Figure 1.7), the role of which brings about the most heated debate.
The activity of these two proteins has been very difficult to quantify. TRPM7 by itself appears to be a Ca²⁺ channel but in the presence of TRPM6 the affinity series of transported cations places Mg²⁺ above Ca²⁺. The differences in reported conductance were caused by the expression patterns of these genes. TRPM7 is expressed in all cell types tested so far, while TRPM6 shows a more restricted pattern of expression. An unfortunate choice of experimental system by Voets et al., (2004) led to the conclusion that TRPM6 is a functional Mg²⁺ transporter. However, later work by Chubanov et al. (2004) clearly showed that TRPM7 is required for TRPM6 activity and that the results of Voets et al. are explained by the expression of TRPM7 in the experimental cell line used by Voets et al. in their experiments. Whether TRPM6 is functional by itself is yet to be determined.
The predicted TM topology of the TPRM6 and TRPM7 proteins has been adapted from Nadler et al. (2001), Runnels et al. (2001) and Montell et al. (2002), this figure shows the computer predicted membrane topology of the TRPM6 and TRPM7 proteins in Homo sapiens. At this time, the topology shown should be considered a tentative hypothesis. The TM domains are shown in light blue, the pore loop in purple, the TRP motif in red and the kinase domain in green. The orientation in the membrane and the positions of the N- and C-termini are indicated and the figure is not drawn to scale.
The conclusions of the Voets et al. (2004) paper are probably incorrect in attributing the Mg²⁺ dependent currents to TRPM7 alone, and their kinetic data are likely to reflect the combined TRPM7/ TRPM6 channel. The report presents a robust collection of data consistent with a channel-like activity passing Mg²⁺, based on both electrophysiological techniques and also mag-fura 2 to determine changes in cytoplasmic free Mg²⁺.
Magnesium transporter