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Molekulare Neurosensorik
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» Forschungszentrum caesar » Molekulare Neurosensorik » Ausgewählte Themen » Cyclic Nucleotide-regulated Channels 

Cyclic Nucleotide-regulated Channels

Cyclic nucleotides, adenosine 3’-5’ cyclic monophosphate (cAMP) and guanosine 3’-5’ cyclic monophosphate (cGMP), are important second messengers that are generated or degraded when cells face external chemical or physical stimuli.

cAMP
cGMP



Figure 1:
  
Chemical representation of the second messenger molecules cAMP and cGMP.

 

Major targets of cyclic nucleotides are cyclic nucleotide-regulated ion channels. These channels transduce the amount of cyclic nucleotides into changes in membrane voltage and conductance. Cyclic nucleotide-regulated ion channels belong to the superfamily of voltage-gated channels due to their membrane topology and oligomeric structure.


Figure 2:
  
Topology and tetrameric arrangement of cyclic nucleotide-regulated channels.

 

Two groups of cyclic nucleotide-regulated ion channels can be distinguished:

1. Cyclic nucleotide-gated (CNG) channels are directly activated by the binding of cyclic nucleotides. These channels are present in photoreceptors, olfactory neurons, and in sperm. We are studying the molecular basis for activation of these channels by biophysical, biochemical, and structural methods.



Figure 3:
  
(Left and middle) CNG channels are present in ciliary structures of photoreceptors and sperm. (Right) Activation of CNG channels in sea urchin sperm evokes a K+-dependent hyperpolarization.

 

2. Hyperpolarization activated and cyclic nucleotid gated (HCN) channels are activated by membrane voltage and their activity is modulated by cyclic nucleotides. These channels are sometimes called pacemaker channels because in heart and brain they are involved in setting the pace of rhythmic oscillations of single cells or networks. We are studying the distribution of HCN channels in the brain with biochemical methods and with confocal microscopy. We are interested in the subunit composition of HCN channels in different tissues.


Figure 4:
  
Expression of HCN channel subunits 1, 3, and 4 in the olfactory bulb. Low magnification of triple-labeling for HCN1 (green), HCN3 (red), and HCN4 (blue) in the external plexiform layer (EPL) and glomerular layer (GL).

 

Furthermore, we have recently been studying the consequence of mutations in HCN channels for cardiac physiology.