Transient receptor potential melastatin 1 (TRPM1) is an ion-conducting plasma membrane channel inhibited by zinc ions.

TRPM1 is the founding member of the melastatin subgroup of transient receptor potential (TRP) proteins, but it has not yet been firmly established that TRPM1 proteins form ion channels. Consequently, the biophysical and pharmacological properties of these proteins are largely unknown. Here we show that heterologous expression of TRPM1 proteins induces ionic conductances that can be activated by extracellular steroid application.

TRPM channels mediate zinc homeostasis and cellular growth during Drosophila larval development.

TRPM channels have emerged as key mediators of diverse physiological functions. However, the ionic permeability relevant to physiological function in vivo remains unclear for most members. We report that the single Drosophila TRPM gene (dTRPM) generates a conductance permeable to divalent cations, especially Zn(2+) and in vivo a loss-of-function mutation in dTRPM disrupts intracellular Zn(2+) homeostasis.

TRPM3 channels provide a regulated influx pathway for zinc in pancreatic beta cells.

Zinc is stored in insulin-containing dense core vesicles of pancreatic beta-cells where it forms crystals together with insulin and calcium ions. Zinc ions are therefore released together with insulin upon exocytosis of these vesicles. Consequently, pancreatic beta-cells need to take up large amounts of zinc from the extracellular space across their plasma membrane.

Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells.

Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level.

Characterization of a proton-activated, outwardly rectifying anion channel.

Anion channels are present in every mammalian cell and serve many different functions, including cell volume regulation, ion transport across epithelia, regulation of membrane potential and vesicular acidification. Here we characterize a proton-activated, outwardly rectifying current endogenously expressed in HEK293 cells. Binding of three to four protons activated the anion permeable channels at external pH below 5.

Isoflurane-induced surgical tolerance mediated only in part by beta3-containing GABA(A) receptors.

The targets which mediate the actions of the volatile general anaesthetic isoflurane are unknown. Based on pharmacological studies using GABA(A) receptor antagonists it has recently been suggested that GABA(A) receptors would not mediate the immobilizing action of isoflurane. Using the beta3(N265M) knock-in mouse model we found that the mutant mice were less sensitive to the immobilizing action of isoflurane, indicating a role of beta3-containing GABA(A) receptors in mediating immobility.

Mutational analysis of molecular requirements for the actions of general anaesthetics at the gamma-aminobutyric acidA receptor subtype, alpha1beta2gamma2.

Background: Amino acids in the beta subunit contribute to the action of general anaesthetics on GABA(A) receptors. We have now characterized the phenotypic effect of two beta subunit mutations in the most abundant GABA(A) receptor subtype, alpha1beta2gamma2.

Results: The beta2(N265M) mutation in M2 decreased the modulatory actions of propofol, etomidate and enflurane, but not of alphaxalone, while the direct actions of propofol, etomidate and alphaxalone were impaired.

General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit.

General anesthetics are widely used in clinical practice. On the molecular level, these compounds have been shown to modulate the activity of various neuronal ion channels. However, the functional relevance of identified sites in mediating essential components of the general anesthetic state, such as immobility and hypnosis, is still unknown.