HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 97/6/3880    most recent 00246.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ouyang, Q. Articles by Harris-Warrick, R. M. Search for Related Content PubMed PubMed Citation Articles by Ouyang, Q. Articles by Harris-Warrick, R. M.

Panulirus interruptus I_h-Channel Gene PIIH: Modification of Channel Properties by Alternative Splicing and Role in Rhythmic Activity

Department of Neurobiology and Behavior, Cornell University, Ithaca, New York

Submitted 6 March 2007; accepted in final form 2 April 2007

We cloned 10 full-length variants of PIIH, the gene for I_h from the spiny lobster, Panulirus interruptus, using reverse transcription-PCR (RT-PCR) and rapid amplification of cDNA ends (RACE). This gene shows a significant amount of alternative splicing in the S3–S4 and S4–S5 linkers, in the P-loop and the entire S6 transmembrane domain, in the cyclic nucleotide binding domain (CNBD), and near the 3' end of the gene. Functional expression of seven splice variants in Xenopus oocytes generated slowly activating hyperpolarization-activated inward currents, which were blocked by the I_h channel blockers CsCl and ZD7288. The different splice variants had markedly varying activation kinetics and voltage dependence of activation. Bath application of 8-Br-cAMP shifted the V_1/2 to more positive potentials and accelerated the activation kinetics in an isoform-specific manner. Two variants containing a segment with an ER-retention motif in the S4-S5 loop did not produce currents in oocytes. Overexpression of one splice variant, PIIH AB_S-I, in pyloric dilator (PD) neurons in the lobster stomatogastric ganglion produced an average threefold increase in I_h without evoking a compensatory increase in I_A. The voltage for half-maximal activation of I_h in PIIH AB_S-I-expressing PDs was shifted in the depolarizing direction by 9 mV, whereas the slope factor decreased by 3.8 mV. Moreover, its activation kinetics were significantly faster than in control PDs. PIIH AB_S-I overexpression enhanced PD neuron rhythmic firing in an amplitude-dependent manner above a minimal threshold two- to threefold increase in amplitude.