Receptors, Ion Channels and Transporters: Basic Mechanisms and Pharmacological Interactions
The expression and physiological properties of receptors, ion channels and transporters shape the electrical and biochemical properties of individual neurons and neural circuits. These membrane proteins are targets for drugs for the treatment of neurological conditions and also interact with addictive drugs such as nicotine, opioids, cocaine and amphetamines. Modern electrophysiological approaches allow the analysis of single receptors and ion channels in real time, revealing their sensitivity to transmitters and drugs, changes in membrane voltage, and physical stimuli such temperature and pressure. Advanced cellular imaging techniques use fluorescent indicators to study ion flux and voltage changes across the neuronal cell membrane. Molecular, biochemical and structural approaches reveal functional domains within ion channels and transporters interacting with neurotransmitters, therapeutic drugs and other neuronal proteins.
Receptors, Ion Channels, and Transporters Image Gallery
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- Calcium dependence of the type I InsP3 receptor. Bezprozvanny et al., Nature 351: 751‑754 , 1991
- Physiological acoustic stimulation reduces the phosphorylation state of the Kv3.1 potassium channel in auditory brainstem neurons. Images show the levels of immunostaining for Kv3.1 specifically phosphorylated at serine 503 in two areas of the brainstem in an animal exposed to sound to one ear only. The nuclei at the top right and bottom left were stimulated by the sensory input and have lower levels of phosphorylated channels (from Song et al., Nature Neurosci., 8: 1335-1342, 2005)
- Activation of Protein Kinase C recruits Cav2.1 calcium channels to the plasma membrane at the distal tips of neurites. Left, Localization of actin (blue), tubulin (red) and Cav2.1 channels (green) in the growth cone of an unstimulated neuron (from a collaboration between the Kaczmarek and Forscher laboratories). Right. Live imaging of Cav2.1 channels (red) and tubulin (green) in a single neuronal growth cone before and after activation of protein kinase C. In response to activation of the enzyme, the channels move to the distal edge of the neurite where they are inserted into the plasma membrane (from Zhang et al., J. Neurosci. 28: 2601-2612, 2008).
- Current elicited with a 1 ms (*a*) or 4 s (*b*) application of 1 mM glutamate from an excised membrane patch containing hundreds of recombinant GluN1/GluN2A receptors. *c,* responses to two 1 ms pulses of 1 mM glutamate (arrowheads) applied at an interval of 300 ms. *d*, /Left/, results from a paired-pulse protocol using 2-s applications of 1 mM glutamate. The peak current evoked by the second application recovers mono-exponentially (solid line). /Right/, early phase of recovery on an expanded time scale. *e*, two groups of consecutive records obtained from a patch containing just one GluN1/GluN2A channel in response to 1 ms applications of 1 mM glutamate (arrowheads). The different mean open times (MOT) during each set of records are indicative of modal gating and result in activations of different durations and ensemble averages that decay with different time-courses. Image from the Howe Lab.