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

In striated muscles, Ca2+ release from internal stores through ryanodine re ceptor (RyR) channels is triggered by functional coupling to voltage-activa ted Ca2+ channels known as dihydropyridine receptors (DHPRs) located in the plasma membrane. In skeletal muscle, this occurs by a direct conformationa l link between the tissue-specific DHPR (Ca-v. 1.1) and RyR(1), whereas in the heart the signal is carried from the cardiac-type DHPR (Ca(v)1.2) to Ry R(2) 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 immun oprecipitated from solubilized rat brain membranes with antibodies against DHPR of the Ca(v)1.2 or Ca(v)1.3 subtypes contain RyR. Only type-1 RyR is c o-precipitated, although the major brain isoform is RyR(2). This suggests t hat, in neurons, DHPRs could communicate with RyRs by way of a strong molec ular interaction and, more generally, that the physical link between DHPR a nd RyR shown to exist in skeletal muscle can be extended to other tissues.