Question: 

In many cell types, depletion of intracellular Ca²⁺-stores results in store-operated Ca²⁺-entry (SOCE) across the cellular membrane. However, the effects of SOCE on membrane excitability and mitochondrial functions in central neurons are not well defined. We explored such cellular downstream effects in hippocampal pyramidal cells.

Methods: 

Experiments were conducted in organotypic hippocampal slice cultures of the rat by applying electrophysiological and live-cell fluorescence imaging techniques.

Results: 

We report that SOCE is associated with (i) elevations of Ca²⁺-concentration in individual neuronal mitochondria ([Ca²⁺]_m). In addition, SOCE can result in (ii) hyperpolarizing neuronal membrane currents, (iii) increase in extracellular K⁺-concentration ([K⁺]_o), (iv) mitochondrial membrane depolarization, and (v) changes in intracellular redox state (NAD(P)H and FAD fluorescence), the latter reflecting responses of energy metabolism. These additional downstream effects of SOCE required concomitant muscarinic receptor activation by carbachol or acetylcholine, and were suppressed by agonist washout or application of antagonist, atropine.

Conclusions: 

We conclude that activation of muscarinic receptors determines the downstream effects of SOCE on neuronal membrane excitability and energy metabolism. This mechanism might have significant impact on information processing and neurometabolic coupling in central neurons.