KCNA10: a novel ion channel functionally related to  both voltage-gated potassium and CNG cation channels

Lang, Rainer; Lee, George; Liu, Weimin; Tian, Shulan; Rafi, Hamid; Orías, Marcelo; Segal, Aaron; Desir, Gary V.

doi:10.1152/ajprenal.2000.278.6.f1013

Cited by 37 publications

(32 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7B). A cGMP-activated K ϩ channel was identified in human collecting duct and proposed as a candidate for the basolateral principal cell K ϩ conductance (16). However, this channel is voltage gated and does not pass inward current, properties quite inconsistent with the basolateral conductance in our study.…”

Section: Principal Cells Of Rat Ccd Have a Large Whole Cell K ϩcontrasting

confidence: 66%

Basolateral K⁺conductance in principal cells of rat CCD

Gray

Frindt

Zhang

et al. 2005

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Whole cell K ϩ current was measured by forming seals on the luminal membrane of principal cells in split-open rat cortical collecting ducts. The mean inward, Ba 2ϩ -sensitive conductance, with 40 mM extracellular K ϩ , was 76 Ϯ 12 and 141 Ϯ 22 nS/cell for animals on control and high-K ϩ diets, respectively. The apical contribution to this was estimated to be 3 and 16 nS/cell on control and high-K ϩ diets, respectively. To isolate the basolateral component of whole cell current, we blocked ROMK channels with either tertiapin-Q or intracellular acidification to pH 6.6. The current was weakly inward rectifying when bath K ϩ was Ն40 mM but became more strongly rectified when bath K ϩ was lowered into the physiological range. Including 1 mM spermine in the pipette moderately increased rectification, but most of the outward current remained. The K ϩ current did not require intracellular Ca 2ϩ and was not inhibited by 3 mM ATP in the pipette. The negative log of the acidic dissociation constant (pKa) was ϳ6. homeostasis by setting the resting potential of the cell. K ϩ flux across the basolateral membrane can be in either direction depending on the physiological setting (22,33). In states where K ϩ conservation is required, for example on a low-K ϩ diet or during neonatal growth, K ϩ entering the cell by the active Na ϩ -K ϩ -ATPase is recycled across the basolateral membrane to prevent losses through apical K ϩ channels. In states of K ϩ excess or in the setting of increased aldosterone, the direction of net K ϩ flux across the basolateral membrane reverses (22, 33) such that K ϩ now enters the cell through the basolateral channels and is then secreted into the urine across the apical membrane. Finally, the basolateral K ϩ conductance influences Na ϩ reabsorption by helping to establish the apical membrane potential.Despite its importance, our knowledge of the molecular determinants that underlie the basolateral K ϩ conductance in principal cells is limited. From perfusion studies of isolated rat CCDs, it has been shown that the basolateral K ϩ conductance is Ba 2ϩ sensitive but TEA insensitive (35) and that the fractional apical resistance with amiloride in the lumen is 0.9 (36). The permeability sequence is K ϩ Ͼ Rb ϩ Ͼ NH 4 ϩ (35). Singlechannel recordings from K ϩ channels on the basolateral membrane are technically challenging as the basement membrane presents a barrier to formation of giga-ohm seals on the basolateral surface of these cells. Two approaches have been used to circumvent this problem: enzymatic digestion of the basement membrane (11) and mechanical removal of the adjacent intercalated cells permitting access to the lateral principal cell membrane (50). After collagenase digestion of the basement membrane, a 148-pS channel (cell attached) that decreased to 85 pS when excised into a low-K ϩ bath and a 67-pS channel (cell attached) that decreased to 28 pS when excised were observed (12). The larger conductance channel was inhibited by intracellular acidification with a negative log of the acidic disso...

show abstract

Section: Principal Cells Of Rat Ccd Have a Large Whole Cell K ϩcontrasting

confidence: 66%

Basolateral K⁺conductance in principal cells of rat CCD

Gray

Frindt

Zhang

et al. 2005

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…However, cngcs have been detected in cell types other than sensory receptor neurons, and have been cloned from a number of different tissue types in animals (Biel et al., 1999b;Finn et al, 1996;Lang et al, 2000), suggesting that their role in multicellular organisms may be more diverse than originally thought. Animal cngcs are characterized by the following functional parameters: They are not, or only weakly, voltage gated; they are activated by direct binding of cyclic nucleotide (cAMP and cGMP); they are selective for cations but do not discriminate between conductance of cations such as Ca 2ϩ , Na ϩ , and K ϩ ; their activation by cyclic nucleotides is blocked by calmodulin; and they show varying degrees of conductance rectification (Zagotta and Siegelbaum, 1996).…”

mentioning

confidence: 99%

Electrophysiological Analysis of Cloned Cyclic Nucleotide-Gated Ion Channels

et al. 2002

View full text Add to dashboard Cite

Electrophysiological studies were conducted on the cloned plant cyclic nucleotide-gated ion channels AtCNGC2 and AtCNGC1 from Arabidopsis, and NtCBP4 from tobacco (Nicotiana tobacum). The nucleotide coding sequences for these proteins were expressed in Xenopus laevis oocytes or HEK 293 cells. Channel characteristics were evaluated using voltage clamp analysis of currents in the presence of cAMP. AtCNGC2 was demonstrated to conduct K ϩ and other monovalent cations, but exclude Na ϩ ; this conductivity profile is unique for any ion channel not possessing the amino acid sequence found in the selectivity filter of K ϩ -selective ion channels. Application of cAMP evoked currents in membrane patches of oocytes injected with AtCNGC2 cRNA. Direct activation of the channel by cyclic nucleotide, demonstrated by application of cyclic nucleotide to patches of membranes expressing such channels, is a hallmark characteristic of this ion channel family. Voltage clamp studies (two-electrode configuration) demonstrated that AtCNGC1 and NtCBP4 are also cyclic nucleotidegated channels. Addition of a lipophilic analog of cAMP to the perfusion bath of oocytes injected with NtCBP4 and AtCNGC1 cRNAs induced inward rectified, noninactivating K ϩ currents.Cyclic nucleotide-gated nonselective cation channels (cngcs) represent a newly identified family of plant ion transport proteins (Kö hler et al., 1999;Leng et al., 1999). This putative family of plant ion channels shares deduced secondary and tertiary structural homology with a diverse family of cngcs cloned and characterized from animal systems (Zagotta and Siegelbaum, 1996). However, primary amino acid sequence homology between this family of plant proteins and their presumed animal homologs is not very great (approximately 22%; Leng et al., 1999).Animal cngcs are primarily, but not in all cases (Lee et al., 2001), expressed in sensory neurons and function in signal transduction systems. However, cngcs have been detected in cell types other than sensory receptor neurons, and have been cloned from a number of different tissue types in animals (Biel et al., 1999b;Finn et al., 1996;Lang et al., 2000), suggesting that their role in multicellular organisms may be more diverse than originally thought. Animal cngcs are characterized by the following functional parameters: They are not, or only weakly, voltage gated; they are activated by direct binding of cyclic nucleotide (cAMP and cGMP); they are selective for cations but do not discriminate between conductance of cations such as Ca 2ϩ , Na ϩ , and K ϩ ; their activation by cyclic nucleotides is blocked by calmodulin; and they show varying degrees of conductance rectification (Zagotta and Siegelbaum, 1996). It is interesting that their relative conductance of specific cations, their relative activation by cAMP versus cGMP, and the extent of their conductance rectification are typically related to the specific role they play in a diverse number of signal transduction pathways and, in addition, other physiological processes in animals.Gen...

show abstract

“…In the present study, we identified one genetic variant in KCNA10 gene and four rare variants in LAMB2 gene which were not identified in our previous GWAS. KCNA10 encodes a recently discovered voltage-gated Potassium (K) channel located in the heart, aorta glomerular endothelium, and apical membrane of renal proximal tubular cells [39,40]. Its presence in endothelial and vascular smooth muscle cells supports the notion that it may also regulate vascular tone [40].…”

Section: Discussionmentioning

confidence: 98%