Molecular identification of Kvα subunits that contribute to the oxygen‐sensitive K⁺ current of chemoreceptor cells of the rabbit carotid body

Abstract

Rabbit carotid body (CB) chemoreceptor cells possess a fast-inactivating K+ current that is specifically inhibited by hypoxia. We have studied the expression of Kvalpha subunits, which might be responsible for this current. RT-PCR experiments identified the expression of Kv1.4, Kv3.4, Kv4.1 and Kv4.3 mRNAs in the rabbit CB. There was no expression of Kv3.3 or Kv4.2 transcripts. Immunocytochemistry with antibodies to tyrosine hydroxylase (anti-TH) and to specific Kv subunits revealed the expression of Kv3.4 and Kv4.3 in chemoreceptor cells, while Kv1.4 was only found in nerve fibres. Kv4.1 mRNA was also found in chemoreceptor cells following in situ hybridization combined with anti-TH antibody labelling. Kv4.1 and Kv4.3 appeared to be present in all chemoreceptor cells, but Kv3.4 was only expressed in a population of them. Electrophysiological experiments applying specific toxins or antibodies demonstrated that both Kv3.4 and Kv4.3 participate in the oxygen-sensitive K+ current of chemoreceptor cells. However, toxin application experiments confirmed a larger contribution of members of the Kv4 subfamily. [Ca2+]i measurements under hypoxic conditions and immunocytochemistry experiments in dispersed CB cells demonstrated the expression of Kv3.4 and Kv4.3 in oxygen-sensitive cells; the presence of Kv3.4 in the chemoreceptor cell membrane was not required for the response to low PO2. In summary, three Kv subunits (Kv3.4, Kv4.1 and Kv4.3) may be involved in the fast-inactivating outward K+ current of rabbit CB chemoreceptor cells. The homogeneous distribution of the Kv4 subunits in chemoreceptor cells, along with their electrophysiological properties, suggest that Kv4.1, Kv4.3, or their heteromultimers, are the molecular correlate of the oxygen-sensitive K+ channel.

Carotid body function in heart failure

“…The hypoxia-sensitive Kv channels in adult rabbit CB encompass those with Kv4.1, and Kv4.3 subunits (Ganfornina & López-Barneo, 1992,Sanchez et al 2002. But the rabbit glomus cells also express the Kv3.4 channel, which appears to be insensitive to hypoxia (Sanchezet al 2002).…”

“…The hypoxia-sensitive K + channels in adult rabbit CB glomus cells are voltage-gated, Ca 2+ -insensitive K + (Kv) channels, which encompass Kv4.1 and Kv4.3 subunits (Ganfornina & López-Barneo, 1992,Sanchez et al 2002. Since Ang II enhances CB chemoreceptor sensitivity to hypoxia , we reasoned that endogenous Ang II blunts the Kv currents (I K ) and affects the sensitivity of Kv channels to hypoxia in the CB glomus cells in the CHF state.…”

Expression of Tandem P Domain K+Channel, TREK-1, in the Rat Carotid Body

“…Several potassium channels show an oxygen-sensing property: TASK-1 in cerebellar granule neurons (Plant et al 2002) and in glomus cells (Buckler et al 2000); TASK1 and TASK-3 in H146 cells (Hartness et al 2001); THIK-1 in glossopharyngeal neurons (Campanucci et al 2003); Kv3.4 and Kv4.3 in rabbit glomus cells (Sanchez et al 2002). However, TREK-1 sensitivity for oxygen is argued.…”

S3b Amino Acid Substitutions and Ancillary Subunits Alter the Affinity of Heteropoda venatoria Toxin 2 for Kv4.3

“…It is one of a diverse group of peptide toxins that form an "inhibitor cystine knot" (ICK) motif (Norton and Pallaghy, 1998). HpTx2 and the nearly identical HpTx3 have been shown to inhibit Kv4-based transient outward currents in the hearts and brains of several mammalian species but to have no apparent effect on other currents, including nonKv4-based transient K ϩ currents, demonstrating the toxin's utility in understanding native transient outward potassium currents (Sanguinetti et al, 1997;Brahmajothi et al, 1999;Guo et al, 1999Guo et al, , 2005Himmel et al, 1999;Kassiri et al, 2002;Ramakers and Storm, 2002;Sanchez et al, 2002;Varga et al, 2004;Aimond et al, 2005;Tang et al, 2005;Lauver et al, 2006;Wang and Schreurs, 2006;Colinas et al, 2008;Nerbonne et al, 2008).…”