TRPM1: The endpoint of the mGluR6 signal transduction cascade in retinal ON-bipolar cells

Oregon Health and Science University, Ophthalmology, Portland, Oregon, USA.
BioEssays (Impact Factor: 4.84). 07/2010; 32(7):609-14. DOI: 10.1002/bies.200900198
Source: PubMed

ABSTRACT For almost 30 years the ion channel that initiates the ON visual pathway in vertebrate vision has remained elusive. Recent findings now indicate that the pathway, which begins with unbinding of glutamate from the metabotropic glutamate receptor 6 (mGluR6), ends with the opening of the transient receptor potential (TRP)M1 cation channel. As a component of the mGluR6 signal transduction pathway, mutations in TRPM1 would be expected to cause congenital stationary night blindness (CSNB), and several such mutations have already been identified in CSNB families. Furthermore, expression of TRPM1 in both the retina and skin raises the possibility that a genetic link exists between certain types of visual and skin disorders.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the widely used mouse model of retinal degeneration, rd1, the loss of photoreceptors leads to rhythmic electrical activity of around 10-16 Hz in the remaining retinal network. Recent studies suggest that this oscillation is formed within the electrically coupled network of AII amacrine cells and ON-bipolar cells. A second mouse model, rd10, displays a delayed onset and slower progression of degeneration, making this mouse strain a better model for human retinitis pigmentosa. In rd10, oscillations occur at a frequency of 3-7 Hz, raising the question whether oscillations have the same origin in the two mouse models. As rd10 is increasingly being used as a model to develop experimental therapies, it is important to understand the mechanisms underlying the spontaneous rhythmic activity. To study the properties of oscillations in rd10 retina we combined multi electrode recordings with pharmacological manipulation of the retinal network. Oscillations were abolished by blockers for ionotropic glutamate receptors and gap junctions. Frequency and amplitude of oscillations were modulated strongly by blockers of inhibitory receptors and to a lesser extent by blockers of HCN channels. In summary, although we found certain differences in the pharmacological modulation of rhythmic activity in rd10 compared to rd1, the overall pattern looked similar. This suggests that the generation of rhythmic activity may underlie similar mechanisms in rd1 and rd10 retina.
    PLoS ONE 06/2014; 9(6):e99075. DOI:10.1371/journal.pone.0099075 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glutamate, the primary excitatory neurotransmitter in the central nervous system (CNS), exerts neuromodulatory actions via the activation of metabotropic glutamate (mGlu) receptors. There are eight known mGlu receptor subtypes (mGlu1-8), which are widely expressed throughout the brain, and are divided into three groups (I-III), based on signalling pathways and pharmacological profiles. Group III mGlu receptors (mGlu4/6/7/8) are primarily, although not exclusively, localised on presynaptic terminals, where they act as both auto- and hetero-receptors, inhibiting the release of neurotransmitter. Until recently, our understanding of the role of individual group III mGlu receptor subtypes was hindered by a lack of subtype-selective pharmacological tools. Recent advances in the development of both orthosteric and allosteric group III-targeting compounds, however, have prompted detailed investigations into the possible functional role of these receptors within the CNS, and revealed their involvement in a number of pathological conditions, such as epilepsy, anxiety and Parkinson's disease. The heterogeneous expression of group III mGlu receptor subtypes throughout the brain, as well as their distinct distribution at glutamatergic and GABAergic synapses, makes them ideal targets for therapeutic intervention. This review summarises the advances in subtype-selective pharmacology, and discusses the individual roles of group III mGlu receptors in physiology, and their potential involvement in disease.
    Neurochemical Research 08/2014; DOI:10.1007/s11064-014-1415-y · 2.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Transient receptor potential (TRP) channels form a diverse family of cation channels comprising 28 members in mammals. Although some TRP proteins can only be found on intracellular membranes, most of the TRP protein isoforms reach the plasma membrane where they form ion channels and control a wide number of biological processes. There, their involvement in the transport of cations such as calcium and sodium has been well documented. However, a growing number of studies have started to expand our understanding of these proteins by showing that they also transport other biologically relevant metal ions like zinc, magnesium, manganese and cobalt. In addition to this newly recognized property, the activity and expression of TRP channels can be regulated by metal ions like magnesium, gadolinium, lanthanum or cisplatin. The aim of this review is to highlight the complex relationship between metal ions and TRP channels.
    Pflügers Archiv - European Journal of Physiology 08/2014; DOI:10.1007/s00424-014-1590-3 · 3.07 Impact Factor


Available from
Apr 10, 2015