known as a phototransduction cascade occurs. It is a signal transduction pathway that leads to the activation of the enzyme phosphodiesterase, which hydrolyzes cGMP into 5’-GMP, decreasing the concentration of cGMP. In the absence of cGMP, the CNG channels in the photoreceptors close preventing the flow of the aforementioned dark current. This in turn causes a hyperpolarization of the outer segment of the photoreceptor, preventing the propagation of an action potential and the release of glutamate. Studies have shown that over activation of cGMP-dependent CNG channels in photoreceptors can lead to their degeneration. If the CNG channels on a photoreceptor are continuously activated, Ca2+ and Na+ ion flux into the outer segment of the photoreceptor will increase so that it depolarizes beyond the dark current. Through a positive feedback loop, this would then increase the current of Ca2+ into the cell. High concentration of Ca2+ in the photoreceptor cell would lead to its death programmed cell death or apoptosis. Retinitis pigmentosa Retinitis Pigmentosa (RP) is a genetic disease in which patients suffer degeneration of rod and cone photoreceptors. The loss starts in the patient's peripheral vision and progresses to the central visual field, leaving the patient blind by middle age. About 1% of RP patients have mutations in cGMP alpha-subunit. Eight mutations have been identified- four are nonsense mutations, one is a deletion that includes most of the transcriptional unit. The other three are missense mutations and frameshift mutations, which lead to a shortening of amino acid sequence in the C terminus. It is still not known why the absence of cGMP-gated cation channels causes photoreceptor degradation. Mutations causing RP have also been found in the rhodopsin gene and in the alpha- and beta-subunits of rod phosphodiesterase, which encode rod phototransduction cascades. The mutation of these subunits indirectly impairs rod cGMP-gated channel function, which implies that there is a common mechanism of photoreceptor degradation. Pacemaker cells In the nervous system, heart, and some visceral organs, cells contain cyclic nucleotide gated channels which determine the rhythm of the organ. These channels, formally called hyperpolarization-activated cyclic nucleotide–gated channels (HCN channels), are also termed "pacemaker channels" because of this critical function. As their name implies, they are open during conditions of hyperpolarization and closed during depolarization. The significance of this in the sinoatrial node (and, as backup, in the atrioventricular node) is that as the heart resets, or hyperpolarizes, after each beat, HCN