Molecular interaction of dihydropyridine receptors with type-1 ryanodine receptors in rat brain

In striated muscles, Ca2+ release from internal stores through ryanodine receptor (RyR) channels is triggered by functional coupling to voltage-activated Ca2+ channels known as dihydropyridine receptors (DHPRs) located in the plasma membrane. In skeletal muscle, this occurs by a direct conformational link between the tissue-specific DHPR (Cav1.1) and RyR1, whereas in the heart the signal is carried from the cardiac-type DHPR (Cav1.2) to RyR2 by calcium ions acting as an activator. Subtypes of both channels are expressed in the central nervous system, but their functions and mechanisms of coupling are still poorly understood. We show here that complexes immunoprecipitated from solubilized rat brain membranes with antibodies against DHPR of the Cav1.2 or Cav1.3 subtypes contain RyR. Only type-1 RyR is co-precipitated, although the major brain isoform is RyR2. This suggests that, in neurons, DHPRs could communicate with RyRs by way of a strong molecular interaction and, more generally, that the physical link between DHPR and RyR shown to exist in skeletal muscle can be extended to other tissues.