Rhythm generation and synchronization (Coworkers, Dr. Dr. Marco Weiergräber, Renate Clemens, Margit Henry):
Molecular mechanisms of rhythm generation and synchronization in neuronal
cells
Within the last years a number of neurological have been proven to be associated
with alterations in voltage- and ligand-gated ion channels, resulting in a new
and dramatically evolving field called channelopathies (Ackerman and Clapham,
1997;Ackerman and Clapham, 1997;Lehmann-Horn and Jurkat-Rott, 1999;Kullmann,
2002). With increasing evidence of ion channels displaying the molecular basis
for identified and yet unidentified channelopathies there is an exceeding
interest to understand the functional interaction of ion channels, especially in
terms of pharmacological treatment and gene therapy.
Channelopathies are also caused by mutations in auxiliary subunits and
interacting proteins as has recently been shown for EFHC1, a protein interacting
with the carboxy terminus of Cav2.3 (Suzuki et al., 2004).
To understand the molecular and cellular basis for how ion channels (R- and
T-type voltage-gated Ca2+ channels) establish or modulate a spontaneous and
rhythmic membrane excitability, we are investigating mouse models lacking either
the R- or a T-type voltage-gated Ca2+ channel, or both. The insight into the
molecular mechanisms will help to elucidate channelopathies related to cardiac
arrhythmia and epilepsies caused by disturbances in thalamocortical –
corticothalamic neuronal circuits. - As channelopathies are also caused by
mutations in auxiliary subunits and because the cloning technique did not give
enough information about the heteromeric nature of ion channel complexes, R- and
T-type channels are purified and interaction partners are determined in heart
and thalamus (more details on E-/R-type Ca2+ channel, rhythm,
synchronization and epilepsy).
References (“rhythm generation and synchronization”)
Ackerman MJ, Clapham DE (1997) Mechanisms of disease - Ion channels - Basic
science and clinical disease. N Engl J Med 336: 1575-1586.
Kullmann DM (2002) The neuronal channelopathies. Brain 125: 1177-1195.
Lehmann-Horn F, Jurkat-Rott K (1999) Voltage-Gated Ion Channels and Hereditary
Disease. Physiological Reviews 79: 1317-1372.
Suzuki T, Delgado-Escueta AV, Aguan K, Alonso ME, Shi J, Hara Y, Nishida M,
Numata T, Medina MT, Takeuchi T, Morita R, Bai D, Ganesh S, Sugimoto Y, Inazawa
J, Bailey JN, Ochoa A, Jara-Prado A, Rasmussen A, Ramos-Peek J, Cordova S,
Rubio-Donnadieu F, Inoue Y, Osawa M, Kaneko S, Oguni H, Mori Y, Yamakawa K
(2004) Mutations in EFHC1 cause juvenile myoclonic epilepsy. Nat Genet.