Tripping the HCN breaker.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability, pacemaking, dendritic integration, and homeostatic plasticity and are culprits in aberrant neuronal activity in certain epilepsies. In this issue of Neuron two manuscripts (Santoro et al. and Zolles et al.

Use-dependent blockade of Cav2.2 voltage-gated calcium channels for neuropathic pain.

The translocation of extracellular calcium (Ca(2+)) via voltage-gated Ca(2+) channels (VGCCs) in neurons is involved in triggering multiple physiological cell functions but also the abnormal, pathophysiological responses that develop as a consequence of injury. In conditions of neuropathic pain, VGCCs are involved in supplying the signal Ca(2+) important for the sustained neuronal firing and neurotransmitter release characteristic of these syndromes. Preclinical data have identified N-type VGCCs (Ca(v)2.

Functional diversity in neuronal voltage-gated calcium channels by alternative splicing of Ca(v)alpha1.

Alternative splicing is a critical mechanism used extensively in the mammalian nervous system to increase the level of diversity that can be achieved by a set of genes. This review focuses on recent studies of voltage-gated calcium (Ca) channel Ca(v)alpha1 subunit splice isoforms in neurons. Voltage-gated Ca channels couple changes in neuronal activity to rapid changes in intracellular Ca levels that in turn regulate an astounding range of cellular processes.