NaV Localization Flashcards
What 2 properties of Nav1.5 contribute to its function in myocardium?
- Fast (within tenths of a microsecond) subsequent opening of Nav1.5 channels triggering excitation-contraction coupling
- Some Nav1.5 channels may re-open during the plateau phase, generating a persistent or “late” inward current
What 4 diseases are linked to Nav1.4?
Myotonia, periodic paralysis, congenital myopathy, and myasthenic syndrome
Which NaV are present in CNS during development and in adult animals?
Nav1.3 is highly expressed in fetal nervous tissues, whereas Nav1.1, Nav1.2, and Nav1.6 are abundant in the adult CNS
Where are Nav1.1 and Nav1.3 localized and what function do they serve in this region?
Nav1.1 and Nav1.3 are localized to the soma of the neuron, where they may control neuronal excitability through integration of synaptic impulses to set the threshold for AP initiation and propagation to the dendritic and axonal compartments.
Where is Nav1.2 expressed?
Unmyelinated axons
Who demonstrated where Nav1.2 expressed and by what method?
Westenbroek et al., 1989
Immunocytochemical experiments
What happens to Nav1.2 during development and what is the significance of this?
Nav1.6 replaces Nav1.2 in maturing nodes of Ranvier
Saltatory conduction
Besides the CNS, where else are Nav1.1 and 1.6 expressed?
Peripheral nervous system
Where were Nav1.7, 1.8 and 1.9 cloned from?
Sympathetic and dorsal root ganglion neurons
What conditions are Nav1.7 linked to?
Paroxysmal extreme pain disorder, chronic inflammatory erythermalgia and congenital insensitivity to pain
Electrophysiological properties of Nav1.7 and importance
Slow inactivation at negative membrane potentials leading to large currents during slow ramp depolarization which contributes to the setting of AP threshold
Electrophysiological properties of Nav1.8 and importance
Nav1.8 has been found to underlie slow inactivating currents in nociceptors and contributes greatly to the upstroke of AP, determining AP frequency in nociceptors.
Effect of Nav1.8 block with what recent subtype specific blocker
Selective block of Nav1.8 with VX-150 has been shown to mitigate against pain in multiple chronic pain conditions (Phase IIb December 2018).
Electrophysiological properties of Nav1.9 and importance
Activates at negative membrane potentials aiding in the setting of resting membrane potential of nociceptors and enteric cells
Implications of Nav1.9 in gastrointestinal system
Nav1.9 has been implicated in inflammatory pain and in particular gastrointestinal conditions with Nav1.9 knockout mice demonstrating attenuated visceral hyperalgesia in response to acute inflammation (Martinez and Mendez, 2008)
