Enhancement of whole cell calcium currents following transient MCAO

Cerebral infarctions have been shown to cause widespread changes of neuronal excitability in non-infarcted tissue. Calcium currents are major determinants of neuronal behavior, and pathological modulation of Ca(2+)-channels is known to lead to altered excitability states in a variety of paradigms. In the present study we addressed the question to what extent whole cell calcium currents are altered after middle cerebral artery occlusion (MCAO) in both the ipsi- and contralateral sensory cortex. Transient middle cerebral artery occlusion was induced for 1 h in rats using the intraluminal thread model. After 7 or 28 days survival, whole cell patch clamp studies were carried out on freshly isolated neurons of the ipsi- and contralateral sensory cortex, and high voltage activated (HVA) calcium currents were examined. In lesioned animals, we found a significant increase of calcium current amplitude and maximal conductance in the sensory cortex contralateral to the infarcts. This was paralleled by a prominent positive shift of the potential of half-maximal activation (V(h,a)) in these cells. Changes were long-lasting and at least stable for the following 28 days. These alterations were present in animals with lesions of moderate size, but not in those with massive infarction, and only in the cortex contralateral to the lesion. Following cortical infarctions, changes of calcium current properties are selectively observed in neurons contralateral to the lesion. At the behavioral level, compensatory mechanisms involving the unaffected hemisphere may induce this alteration of calcium current properties.