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L Salkoff

Publications and source records attributed to L Salkoff.

51 records · Page 3Linked to original sources
PubMed1990

The Drosophila Shaker gene codes for a distinctive K+ current in a subset of neurons.

A transient K+ current coded by the Shaker gene was identified in muscle and expressed in Xenopus oocytes by injecting cRNA transcribed from a cloned cDNA. The Shaker current has not previously been identified in neurons. Mutational analysis now reveals that in neurons, Shaker is required for expression of a very rapidly inactivating K+ current with a depolarized steady-state inactivation curve. Together, these properties distinguish the Shaker-coded current from similar fast transient K+ currents coded by other genes. The Sh5 mutation further enhanced the depolarization of the Shaker current steady-state inactivation curve. Deletion of the Shaker gene completely removes the transient K+ current from a small percentage of neurons (15%) in a mixed population, and removes a portion of the whole-cell current in about 35% of neurons. The remaining 50% of neurons were apparently unaffected by deletion of the Shaker gene. The unique combination of rapid inactivation and depolarized steady-state inactivation of the Shaker current may reflect a unique functional role for this current in the nervous system such as the rapid repolarization of action potentials.

Action Potentials↗
PubMed1989

A family of putative potassium channel genes in Drosophila.

Mutant flies in which the gene coding for the Shaker potassium channel is deleted still have potassium currents similar to those coded by the Shaker gene. This suggests the presence of a family of Shaker-like genes in Drosophila. By using a Shaker complementary DNA probe and low-stringency hybridization, three additional family members have now been isolated, Shab, Shaw, and Shal. The Shaker family genes are not clustered in the genome. The deduced proteins of Shab, Shaw, and Shal have high homology to the Shaker protein; the sequence identity of the integral membrane portions is greater than 50 percent. These genes are organized similarly to Shaker in that only a single homology domain containing six presumed membrane-spanning segments common to all voltage-gated ion channels is coded by each messenger RNA. Thus, potassium channel diversity could result from an extended gene family, as well as from alternate splicing of the Shaker primary transcript.

Amino Acid Sequence↗
PubMed1987

Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila.

The deduced amino acid sequence of a Drosophila gene isolated with a vertebrate sodium channel complementary DNA probe revealed an organization virtually identical to the vertebrate sodium channel protein; four homologous domains containing all putative membrane-spanning regions are repeated in tandem with connecting linkers of various sizes. All areas of the protein presumed to be critical for channel function show high evolutionary conservation. These include those proposed to function in voltage-sensitive gating, inactivation, and ion selectivity. All 24 putative gating charges of the vertebrate protein are in identical positions in the Drosophila gene. Ten introns interrupt the coding regions of the four homology units; introns with positions conserved among homology units bracket a region hypothesized to be the selectivity filter for the channel. The Drosophila gene maps to the right arm of the second chromosome in region 60D-E. This position does not coincide with any known mutations that confer behavioral phenotypes, but is close to the seizure locus (60A-B), which has been hypothesized to code for a voltage-sensitive sodium channel.

Amino Acid Sequence↗
PubMed1986

Occult Drosophila calcium channels and twinning of calcium and voltage-activated potassium channels.

In the membrane of the flight muscle cells of developing Drosophila a large calcium-sensitive potassium current, IKc, was found. It was present before the development of voltage-activated potassium channels and seems to be the first potassium current to develop in the membrane. Also present in these early cells were large numbers of occult (hidden) calcium channels, which remained inactive until the end of pupal development. These inactive calcium channels could be made to function by injecting adenosine triphosphate or ethyleneglycol tetraacetic acid into the early cells. IKc has kinetic properties resembling the later developing voltage-sensitive current IKv, and is distinct from the fast, transient calcium-dependent outward current IAc, which appears much later in development. IAc closely resembles the voltage-sensitive current IAv, also present in these cells. Thus, both of the voltage-sensitive potassium channel types, IAv and IKv, have similar calcium-sensitive counterparts, IAc and IKc, that are present in the same cells.

Action Potentials↗
PubMed1985

Development of ion channels in the flight muscles of Drosophila.

An entire picture of developing membrane electrical properties can be observed in the flight muscles (DLM) of Drosophila. The developmental history of membrane electrogenesis begins in the mid-pupal period and extends into the second day of adult life. Of five prominent extra-junctional ion currents which can be observed, only two are clearly mature before the adult ecloses from the pupal case. These are the two voltage-activated potassium currents, a fast transient current, and a slowly activating current. A fast transient calcium current rapidly develops around the time of adult eclosion. Suprisingly, two more ion currents develop in the adult stage: a fast transient Ca2+-activated potassium current develops during the first few hours of adult life, and a slow noninactivating inward current develops during the following two days. Both the earlier and later developing potassium currents of the transient type function in the role of fast spike repolarization in the adult. However, the later developing current appears to largely supplant the earlier developing current in this role. Thus, Shaker mutants which specifically lack the earlier developing K+ current, nevertheless, have normal appearing action potentials in mature muscle cells.

Animals↗
PubMed1983

Genetic and voltage-clamp analysis of a Drosophila potassium channel.

These genetic and voltage-clamp studies have produced evidence that strongly supports the hypothesis that the Shaker locus codes for at least one molecular component of the IA channel. Mutations at the Shaker locus have effects that are specific to IA, and thus a general membrane component is not produced by this locus. Regarding the function of the Shaker product itself, there is evidence that it is at least involved in the inactivation and recovery process of the channel. The evidence so far is also consistent with there being a single Shaker product per channel. Regarding its genetic and developmental properties, IA is apparently completely independent of the other major voltage-activated K+ channel in the membrane, IK. However, only after molecular information becomes available will it become clear whether or not these experiments have revealed clues about the molecular nature of these channels. Ultimately, voltage-clamp experiments, even combined with resourceful genetic tools, can only reveal circumstantial information about the molecular structure of channels. It is hoped, however, that these studies have stimulated interest in the Shaker locus and that the way has been well prepared for molecular studies of the IA channel. The actual molecular characterization of the Shaker locus is already under way (cf. Jan et al., this volume; M. Tanouye , pers. comm .).

Animals↗
PubMed1982

The mathematics of mosaic analysis. II. Formulae for interacting foci.

Mosaic fate mapping requires first a measurement of the frequency of separation (by genotype) of two structures and then a conversion of this frequency of separation to distance (WYMAN and THOMAS 1982). If the genotype of two structures is visible, the frequency of separation (sturt distance) may be directly obtained. If the genotype is not visible (e.g., for behavioral foci) then the frequency of separation (sturt distance) itself must be calculated. The formulae introduced by HOTTA and BENZER (1972) for calculating frequency of separation are appropriate only for a set of mosaics in which each fly has half normal and half mutant tissue. Using these formulae for a set of mosaics with a different fraction of mutant tissue can give enormously incorrect results.--In this paper we use intuitive lines of reasoning to obtain simple formulae for frequencies of separation that are algebraically equal to the more elaborate HOTTA and BENZER (1972) formulae.--We show that when calculating sturt distances, data from a collection of mosaics with a range of malenesses, even if the average maleness is 1/2, cannot be lumped together. We prove that applying any formula appropriate for m = 1/2 to a set of mosaics all of maleness m, and then to a set of maleness 1-m, and then averaging the two results, does give the correct value for sturt distances. In this way all the mapping distances may be obtained.--Another method for locating foci is called "contour mapping". We show that the currently available contour formulae are inaccurate. We suggest that contour maps be drawn using the accurate sturt distances.

Animals↗
PubMed1981

Outward currents in developing Drosophila flight muscle.

The development of two different voltage-sensitive potassium channels was studied in Drosophila flight muscle by voltage clamp techniques. Early in development active channels are not present in the membrane. The first channels to appear are the A current channels, which carry a fast, rapidly inactivating potassium current. The channels for delayed rectification appear later. Channels carrying inward current also appear only after the A current channels. During development, the A current may be easily studied in isolation from other currents and thus provides a desirable system for studying the genetic determinants of this current.

Animals↗
PubMed1980

Facilitation of membrane electrical excitability in Drosophila.

Prior electrical activity in the indirect flight muscles of Drosophila facilitates membrane excitability. The mechanism of facilitation involves the inactivation of an early, fast, transient outward current by prior membrane depolarizaton. In the facilitated state the calcium-dependent spike-like response has a decreased current and voltage threshold. The facilitated state persists for 1.5 sec after a membrane active response. A single nerve-driven spike is sufficient to facilitate membrane excitability.

Action Potentials↗
PubMedDate not supplied

Drosophila mutants reveal two components of fast outward current.

The gating of potassium ion channels has been shown to be dependent on voltage or Ca2+ ions or both 4,5. A fast transient potassium current (sometimes denoted IA) is found in a wide variety of animals. The Ca2+-sensitivity of this early outward current has been a matter of dispute as reports from different systems have indicated complete insensitivity, marked sensitivity or only partial sensitivity. It is possible that there are two distinct early outward current systems, one Ca2+-sensitive and the other not. Thus, the reports of partial Ca2+-sensitivity would indicate the presence of both systems in the membrane. I now report that in the adult Drosophila flight muscles, the transient outward current is also partially Ca2+-sensitive. The hypothesis that two separate currents are present is strengthened by the discovery that in several mutants of the X-linked Shaker locus (ShKS133, Sh102 and ShK0120): the Ca2+-independent component (IAci) is absent with only the Ca2+-dependent component (IAcd) remaining. Hence, the mutations seem to delete one of two separate current systems. An alternative hypothesis is that only one channel type is present that can be modified by mutation to be totally Ca2+-dependent.

Aminopyridines↗