A surprising ¢nding of these studies was that the direction
of modulation di¡ers between the two K1 subunits. Coexpression
of L subunits accelerated recovery of the cyCav1 subunit,
but slowed recovery of the hCav2.3 isoform. cyCav1, a homologue
of mammalian L-type K1 subunits, exhibits signi¢cant
variation in the cytoplasmic loop between domains I and II
that contains the primary site for L subunit binding, but is
clearly modulated by all three mammalian L subunits studied.
Thus, the recovery of mammalian L-type K1 subunits may be
accelerated by certain L subunit isoforms in a similar manner.
The degree of modulation exerted by each L subtype also
di¡ered between the two K1 subunits. cyCav1 recovered
most quickly in the presence of the cyL subunit, followed by
L3 and L4, which produced comparable enhancement, and the
e¡ect of L2a was seen only at strongly polarized interpulse
potentials. In contrast, the L3 subtype had a more marked
e¡ect upon the hCav2.3 subunit than L4, which was similar
to cyL, and L2a had essentially no e¡ect on recovery. The
order of potency of the three mammalian L isoforms on the
recovery of hCav2.3 is similar to that exerted on preferential
closed-state inactivation of the Cav2.2 subunit [23]. Because
closed-state inactivation re£ects the ease of transition from an
intermediate closed state to an inactivated state, whereas recovery
from inactivation represents the transition from an
inactivated state to a closed state from which the channel
can again be activated, L subunits may a¡ect the modulation
of the two responses via a similar mechanism.
A surprising ¢nding of these studies was that the directionof modulation di¡ers between the two K1 subunits. Coexpressionof L subunits accelerated recovery of the cyCav1 subunit,but slowed recovery of the hCav2.3 isoform. cyCav1, a homologueof mammalian L-type K1 subunits, exhibits signi¢cantvariation in the cytoplasmic loop between domains I and IIthat contains the primary site for L subunit binding, but isclearly modulated by all three mammalian L subunits studied.Thus, the recovery of mammalian L-type K1 subunits may beaccelerated by certain L subunit isoforms in a similar manner.The degree of modulation exerted by each L subtype alsodi¡ered between the two K1 subunits. cyCav1 recoveredmost quickly in the presence of the cyL subunit, followed byL3 and L4, which produced comparable enhancement, and thee¡ect of L2a was seen only at strongly polarized interpulsepotentials. In contrast, the L3 subtype had a more markede¡ect upon the hCav2.3 subunit than L4, which was similarto cyL, and L2a had essentially no e¡ect on recovery. Theorder of potency of the three mammalian L isoforms on therecovery of hCav2.3 is similar to that exerted on preferentialclosed-state inactivation of the Cav2.2 subunit [23]. Becauseclosed-state inactivation re£ects the ease of transition from anintermediate closed state to an inactivated state, whereas recoveryfrom inactivation represents the transition from aninactivated state to a closed state from which the channel
can again be activated, L subunits may a¡ect the modulation
of the two responses via a similar mechanism.
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