These voltage-gated channels initiate action potentials in excitable cells. Local anesthetics such as lidocaine block Na+ channels and have been used to manage cardiac arrhythmias, and non-specific drug binding to the SCN5A channel can alter normal cardiac rhythm.
hERG channels critically contribute to cardiac repolarization. Drugs blocking these channels can lead to a prolongation of the action potential. Also, inhibition of hERG due to unwanted drug side effects means a significant risk factor for cardiac safety.
Mutations in these ion channels lead to disorders that may increase the risk of death from cardiac arrhythmia (long QT syndrome or LQTS) and Jervell and Lange-Nielsen syndrome, associated with congenital deafness.
Kv4.3 channels display rapidly inactivating K+ currents in brain and heart, which regulate neuronal firing and heart pacing. Altered Kv4.3 expression occurs under pathological conditions like heart failure.
nAChRs play a key role in the signal transmission between cells at the nerve/muscle synapses. Various studies demonstrated their involvement in high brain functions and in important neurodegenerative pathologies.
The Na/K-ATPase or Na-pump is the pharmacological receptor for cardiac glycosides, which are widely used in the treatment of heart failure. Furthermore, it is possibly also the physiological receptor for endogenous ouabain compounds.