Question: 

Voltage-gated L-type calcium channels in heart and vascular smooth muscle are a well-established drug target for organic calcium channel blockers since decades and are valuable therapeutics to treat hypertension and myocardial ischemia. Based on recent studies L-type calcium channels may also serve as a potential target for the treatment of Parkinsons disease.

Methods: 

Using unique animal models we and others have revealed the important role of one particular subtype of L-type calcium channels, Cav1.3, in many physiological processes, including neuronal function.

Results: 

Recent data strongly suggest that Cav1.3 mediates calcium transients in dopaminergic substantia nigra pacemaker neurons which may underlie the high susceptibility of these neurons to neurodegeneration in Parkinsons disease. Selective Cav1.3 channel blockers are therefore pursued as novel neuroprotective agents for Parkinsons disease therapy. However, these channels are also expressed in other neurons, endocrine cells, sensory cells, and the heart. Using unique animal models we have shown that Cav1.3 serves as sinoatrial node pacemaker channel, triggers excitation-secretion coupling in cochlear hair cells, and regulates neuronal excitability. Cav1.3 therefore is not only required for normal cardiac automaticity and hearing, but also for emotional and drug taking behaviors.

Conclusion: 

This presentation will provide an overview about the physiological role of Cav1.3 channels and address the important question about potential side effects of Cav1.3-selective blockers as well as their potential for the treatment of other diseases in addition to Parkinsons disease.

Support: 

Austrian Science Fund (P20670, SFB-F44).