Nuclear electrophysiology

Conclusions Patch-clamp, fluorescence microscopy and high-resolution EM have yielded new data which question current concepts of ion transport across the nuclear envelope. The current challenge is to prove that NICs play an important role in nuclear function either through their identity with NPCs or parts thereof. Electrophysiological designs must incorporate cell biology approaches as done for putative protein-conducting channels of the ER (Simon & Blobel, 1991, 1992).Preliminary studies (J.O. Bustamante et al., in preparation), illustrated in Fig. 1, confirm that, as is the case of NPCs, NICs cannot function in an extracellular environment deprived of cytosolic factors. Our current efforts aim at clarifying if the lysate factors required for macromolecular transport through NPCs (e.g., Adam et al., 199la,b) are those required for NIC open-shut gating. Monoclonal antibodies to identified NPC proteins should be helpful in furthering the identification of NICs with NPCs. Our observation of blockade of NIC activity with wheat germ agglutinin, discussed above, supports the idea that NPCs are the structural foundation for NICs. Should NICs be identified with NPCs or otherwise proven essential to nucleocytoplasmic transport, NIC response to cytoplasmic signals would suggest that they are relevant to mediating gene control by transduction and other cytosolic signals (Karin, 1991; Davis, 1992). NIC influence on intranuclear free ion concentrations is potentially important to controlling gene activation, repression, as well as the efficiency and fidelity of gene expression (e.g., Kroeger, 1963; Lezzi & Gilbert, 1970; Leake et al., 1972; Morgan & Curran, 1986; Li & Rokita, 1991; Lippard, 1993). As electrophysiological and cell/molecular biology approaches merge, the prospects improve for the field of nuclear electrophysiology.The author thanks (in alphabetical order) the intellectual contributions of Drs. Christopher W. Akey, Gregory S. Beckler (Promega), Louis J. DeFelice, Colin Dingwall, Alexander Fabiato, Julio M. Fernández, Larry Gerace, John A. Hanover, Bertil Hille, Stuart L. Jacobson, W. Jonathan Lederer, Andrejs Liepins, Gilbert N. Ling, Michele Mazzanti, Ernst Niggli, Sanford M. Simon, Walter Stühmer, and W. Gil Wier. Special thanks are tendered to Drs. Dingwall, Gerace, Hanover and Liepins for their observations on nuclear electrophysiology within the context of cell/molecular biology. Thanks are also extended to Drs. Lederer and Wier for discussions on fluorescence microscopy of Ca²⁺ transients. Dr. Niggli provided the preprint of his paper, with P. Lipp, confirming previous observations that cardiomyocyte nuclei behave as a barrier to intracellular Ca²⁺ waves. Drs. DeFelice and Mazzanti provided a draft of their review on the biophysics of the nuclear envelope. This work is supported by the American Heart Association, Maryland Affiliate. Institutional support and facilities have come through Drs. C. William Balke, Michael R. Gold, W. Gil Wier and W. Jonathan Lederer, to whom the author is deeply grateful. This work is dedicated to my parents for introducing me to scientific curiosity and for their constant incentive and support. A special dedication to my father who recently passed away.