Functional role of the β subunit of high conductance calcium-activated potassium channels

Abstract

Mammalian high conductance, calcium-activated potassium (maxi-K) channels are composed of two dissimilar subunits, alpha and beta. We have examined the functional contribution of the beta subunit to the properties of maxi-K channels expressed heterologously in Xenopus oocytes. Channels from oocytes injected with cRNAs encoding both alpha and beta subunits were much more sensitive to activation by voltage and calcium than channels composed of the alpha subunit alone, while expression levels, single-channel conductance, and ionic selectivity appeared unaffected. Channels from oocytes expressing both subunits were sensitive to DHS-I, a potent agonist of native maxi-K channels, whereas channels composed of the alpha subunit alone were insensitive. Thus, alpha and beta subunits together contribute to the functional properties of expressed maxi-K channels. Regulation of co-assembly might contribute to the functional diversity noted among members of this family of potassium channels.

A calcium switch for the functional coupling between α (hslo) and β subunits (KV, Caβ) of maxi K channels

“…It came to our attention, however, that expressed currents recorded in the cell-attached mode, where [Ca2+]i is in the nM range, showed no difference in Ft/2 when coinjectod with the p subunit, The estimated Fz/2 value (see section 2) was 221:1:19 mV (n=6) when the o pore.forming subunit alone was expressed compared to 21 $ :! : 13 mV (n: 5) when both (z and p subunits were co-injected z, When the same patches were excised and exposed to 10 pM [Ca2+]t, a huge increase in current and a prominent shift in Vz/2 were observed as illustrated in Fig, I, These experiments show that ct and p subtMcManus et ai, [3] using the bovine p subunit and msloi9 oh. Although there is no change in open probability of the channel at resting calcium in the presence of the J] wbunit, ti~e activation kinetics of the currents is altered (see in let in Fig.…”

“…MaxiK channels are unique because they are modulated not only by voltage, but also by calcium in the micromolar range, For this reason it has been proposed that they play a role in the repolarization phase of the action potential and in setting the pace of cell firing in neurons. This type of K channels is ~nformed by at least two subunits, the pore-forming a subunit [I] and a regulatory {$ subunit [2][3][4]. Unlike other voltage-dependent K channel is subunits (Kvis), which are cytoplasmic [5], the iS subunit of the MaxiK channel (Kv,c~l~) has two putative transmembrane regions [2] similar to the 'ripe pars sodium channel subunit [6].…”

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K+Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

“…The cytoplasmic regulatory subunit K v ␤2 associates with Shaker-like K v channels and increases their surface expression in heterologous systems (Shi et al, 1996) while exerting small effects on channel activity (Rettig et al, 1994;Heinemann et al, 1996). In addition to regulating K ϩ channels through chaperone activity or altering gating kinetics, some channel subunits, such as the SUR1 subunit of K ir 6.2 channels or the ␤1 subunits of Slo channels, alter the sensitivities of their associated channels to activating signals, such as voltage, ATP, or Ca 2ϩ (McManus et al, 1995;Tucker et al, 1997).…”

Hypoxia Inducible Factor-2α Stabilization and Maxi-K + Channel β 1 -Subunit Gene Repression by Hypoxia in Cardiac Myocytes

“…14 The ␤ 1 -subunit modifies the Ca 2ϩ and voltage sensitivity of the pore-forming ␣-subunit, and its inhibition results in vasoconstriction. 13,15 The mechanism whereby hypoxia downregulates the ␤ 1 -subunit gene is unknown.…”