Synaptic transmission: ion currents
Synaptic transmission: ion currents Synaptic transmission is an electrical movement within synapses caused by apropagation of nerve impulses (action potentials). Sodium and potassium are the principalions involved in action potential, calcium and chlorine are also engaged. Generally,inward sodium current is associated with the rising phase of the action potential.Voltage-gated sodium channels are responsible for driving neuronal excitability in boththe central and peripheral nervous system. Voltage-sensitive sodium channels areheteromeric complexes consisting of a large central pore-forming glycosylated alphasubunit and two auxiliary beta subunits. Beta subunits regulate channel gating. Sodiumchannel voltage-gated, type I alpha subunit ( Na(v) I alpha ), Sodium channelvoltage-gated type II alpha subunit ( SCN2A ), and Sodium channel voltage gatedtype VIII alpha subunit ( Nav1.6 ), are expressed at high levels in the centralnervous system (CNS). Three isoforms known as Sodium channel voltage-gated type IX alphasubunit ( SCN9A ), Sodium channel voltage-gated type X alpha subunit (SCN10A ) and Sodium channel voltage-gated type XI alpha subunit ( Nav1.9 )are expressed primarily in the peripheral nervous system , . Unlike most voltage-gated channels, Hyperpolarization-activated cation channels of theHCN gene family, such as Hyperpolarization activated cyclic nucleotide-gated potassiumchannel 4 ( HCN4 ), are activated by hyperpolarizing voltage steps to negativepotentials as low as -60 mV, i.e., near the resting potentials of most cells. The HCNchannels are regulated by cyclic nucleotides and conduct both Na+ and K+ ions. Activationof the channel at typical resting potentials results in a net inward current formedlargely by Na+. This current causes depolarization of the membrane toward the thresholdfor firing of an action potential. HCN channels contribute to spontaneous rhythmicactivity in the brain. Ih-current provided by these channels plays important role insensory transduction of visual, taste and olfactory stimuli , . Amiloride-sensitive cation channel 1 ( BnaC2(ASIC1a) ) belongs to the group ofproton-activated and therefore acid-sensing ion channels (ASICs). Typical ASIC currentdisplays a Na+/K+ selectivity ratio d10. ASICs show some permeability to Ca2+. ASICchannels are believed to be involved in pain perception, especially following tissueacidosis . Potassium outflow provides cell repolarisation and return to the resting potential.Outward potassium currents are mediated by different types of channels. Superfamily ofvoltage-gated potassium channels (Kv) is the largest group of proteins catalyzing thetransmembraneous potassium flow. The superfamily of Kv-alpha subunits can be subdividedinto three major families. The first family is the Shaker-related Kv-alpha subunits(Kv1.x....Kv9.x), the second is the ether-a-go-go -related Kv-alpha subunits (KCNH), thethird is the KCNQ-related Kv-alpha subunits. Kv subunits can form heteromultimers and, inaddition, can assemble with various auxiliary subunits. A wide range of potassiumcurrents could be mediated through these ensembles , .KCNQ2, KCNQ3, and possibly KCNQ5 are involved in the widelydistributed in neurons potassium M-current . Outward potassium currents can be activated by various stimuli including rise ofintracellular calcium. Three broad families of calcium-activated potassium channel havebeen identified up to date. These are the family of potassium large conductancecalcium-activated channel that includes Potassium large conductance calcium-activatedchannel, subfamily M, alpha member 1 ( MaxiK alpha ), and the families ofPotassium small conductance calcium-activated channels ( SK1, SK3 ) andpotassium intermediate conductance calcium-activated channels. Calcium-activatedpotassium currents are known to mediate different phases of after-hyperpolarization thatoccurs in neurons coming after generation of the action potential .