Inward Rectification

Inward Rectification refers to decreased conductance upon membrane depolarization. In classical inward rectifier K+ channels, rectification is strong and currents rapidly decline at membrane potentials positive to the reversal potential, in contrast to other Kir channels in which rectification is weak and currents decline only gradually at potentials positive to the reversal potential. 

Inward Rectifier K+ Channels. Figure 2 High [K+] inside cells relative to outside results in normal rectification, whereby outward (positive by convention) potassium currents (/) when cells are depolarized (is positive relative to EK), are biggerthan inward (negative) currents at hyperpolarized (negative) voltages. Inward or anomalous rectifiers show strong or weak inward rectification whereby outward currents are smaller than inward currents. 

The inward rectifier K+ channels (Kir) represent this family of channels that conduct K+ ions preferentially in the inward direction than outward. The occlusion of internal vestibule oftheporeby Mg2+ and polyamines contribute to this inward rectification. These channels... 

Vandeberg, C.A. (1987). Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions. Proc. Natl Acad. Sci. USA 84, 2560-2564. 

I/R, inward rectification O/R, outward rectification CPA, cyclopiazonic acid TG, thapsigargin CCh, carbamylcholine CIF, Ca2+ influx factor CAM-ant., calmodulin antagonist W/C, whole-cell recording C/A, cell-attached recording P-W/C, perforated whole-cell recording. 

Electrophysiological studies on rat hippocampal neurons show two types of KAR with different current responses to KA. In the KA1 response, KA causes little increase in membrane Ca2+ permeability and an outward rectification in the current-voltage plots. The KA2 response is characterized by prominent Ca2+ permeability and an inward rectification in the current voltage plots (Ozawa et al., 1991). 

The 5-HT1A receptors are coupled to potassium and calcium channels. Intracellular current-clamp recordings in slices containing the DR established that the 5-HT-mediated inhibition involved an increase in potassium conductance, which exhibits inward rectification (18,58). This induced a membrane hyperpolarization leading to a decrease in action potential frequency. Similar responses to 5-HT1A receptor activation have been reported in other neuronal types, such as hippocampal pyramidal cells (16,59) or 5-HT neurons of the caudal raphe nuclei (60). 

Loussouarn, G., Marton, L.J., Nichols, C.G. Molecular basis of inward rectification structural features of the blocker defined by extended polyamine analogs. Mol Pharmacol 68 (2005) 298-304. 

In striatal neurons, the effects of D2 receptor activation on K+ channels are more complex. Stimulation of the D2 receptor has been reported to open a K+ channel that displays a 85 pS conductance and a weak inward rectification, and this rectification seems to differ from that found in pituitary cells (Freedman and Weight, 1988 Einhorn et al., 1991 Greif et al., 1995). In contrast, D2 receptor activation was also reported to suppress K+ currents probably through Kir2 channels (Uchimura and North, 1990). However, the activation of K+ channels occurs in a membrane-delimited manner via Gpy mobilization, whereas inhibition of K+ channels could result from the D2 receptor mediated inhibition of adenylyl cyclase and the dephosphorylation of Kir2 subunit at its PKA sensitive site (Nicola et al., 2000). 

As noted in Table 3, the current responsible for inward rectification, IKir (Mermelstein et al., 1998), is increased by D1 receptor activation (Galarraga et al., 1994 Pacheco-Cano et al., 1996). In contrast, D2 receptors suppress IKir currents (Uchimura and North, 1990) although they also activate a low conductance channel (Freedman and Weight, 1988, 1989 Greif et al., 1995 Lin et al., 1998 Waszczak et al., 1998). Thus, dopamine acting via D1... 

Leech CA, Stanfield PR (1981) Inward rectification in frog skeletal muscle fibres and its dependence on membrane potential and external potassium. J Physiol 579 295-309. 

Uchimura N, Cherubini E, North RA (1989) Inward rectification in rat nucleus accumbens neurons. 

Smith PL, Baukrowitz T, Yellen G. 1996. The inward rectification mechanism ofthe HERG cardiac potassium channel. Nature 379 833-36... 

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