Changes in cardiac myocyte morphology alter the properties of voltage-gated ion channels.
OBJECTIVE
The goal of this study was to determine if the properties of the transient outward potassium (I(to)), TTX-resistant sodium (I(Na)) and L-type calcium (I(Ca)) currents are altered during changes in cardiac cell shape.


METHODS
Ventricular myocytes were isolated from 3- to 4-day-old neonatal rats and cultured on either non-aligned or aligned collagen thin gels. In contrast to the flat, stellar-shaped myocytes obtained when the cells are plated on non-aligned collagen gels, myocytes plated on aligned gels display an elongated, rod-like shape. Ion channel expression was measured using the whole-cell arrangement of the patch clamp technique and Western blot analysis.


RESULTS
Peak values for I(to), I(Na) and I(Ca) were 9+/-1, 71+/-13 and 7+/-1 pA/pF, respectively, in the flat cells, and increased to 21+/-2, 190+/-26 and 13+/-1 pA/pF, respectively, in the aligned cells. Application of forskolin (2 microM) and 3-isobutyl-1-methylxanthine (100 microM) resulted in a 101+/-18% increase in I(Ca) in the flat cells, but increased the current by only 43+/-9% in the aligned cells. Internal dialysis of the myocytes with cAMP strongly increased the peak I(Ca) in the flat cells, but caused no significant change in the aligned cells. While both basal and forskolin-stimulated levels of cAMP were the same in the two cell morphologies, the expression of the calcium channel alpha(1C) subunit was increased in the aligned cells.


CONCLUSIONS
The expression and regulatory properties of voltage-gated calcium channels are modified during changes in neonatal rat myocyte shape.
Walsh
Kenneth B
KB
Department of Pharmacology, University of South Carolina, School of Medicine, Columbia 29208, USA. walsh@med.sc.edu
Parks
Graham E
GE
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D020746:Calcium Channels, L-Type / Q000378:metabolism; D018929:Cell Culture Techniques; D048429:Cell Size; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D015222:Sodium Channels / Q000378:metabolism
D020746:Calcium Channels, L-Type; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D015056:1-Methyl-3-isobutylxanthine