Leonard Konrad Kaczmarek PhD
Professor of Pharmacology and of Cellular and Molecular Physiology
Neuroscience; Learning and memory; Ion channels
Research in our laboratory is aimed at understanding the nature of the biochemical changes that occur in neurons and that result in prolonged changes in the behavior of an animal or in its ability to detect specific patterns of sensory inputs. It is known that alterations of the intrinsic electrical excitability of specific neurons are the key feature of such events, and that these are caused by the short-term and long-term regulation of proteins termed ion channels. Our laboratory has isolated the genes for multiple ion channels, and is studying both how these channels function to in the normal nervous system, and how human mutations in these channels give rise to several neurological conditions that produce severe intellectual disability.
Extensive Research Description
Our laboratory has investigates the role of potassium channels, as well as other classes of ion channels, in the short-term and long-term regulation of neuronal excitability. Our group was the first to demonstrate directly, using purified enzymes, that excitability of neurons is regulated by cyclic AMP-dependent protein kinase, protein kinase C and tyrosine phosphatases. As part of this work we isolated the genes for over fourteen novel ion channels and were the first to identify the “two-pore” family of potassium channels. Among the channels that our group cloned and characterized are Kv3.1b channel, which is required for high-frequency firing in many neurons and the Slack and Slick genes that underlie Na+-activated K+ channels. Our work was the first to show directly that rapid changes in the phosphorylation state of ion channels and in the synthesis of new channels occur in vivo in response to changes in an animal’s environment. Most recently, we have found that the Slack protein interacts with the Fragile X Mental Retardation Protein FMRP and that human mutations in Slack produce very severe epilepsy and developmental delay. This is now a major focus of our laboratory.