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-Ca) and L-type calcium Currents are altered during changes in cardiac cell shape. Methods: Ventricular myocytes were isolated front 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 in 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 L ells. Application of forskolin (2 muM) and 3-isobutyl-1-methylxanthine (100 muM) resulted in a 101+/-18% increase in I-Ca in the flat cells, hut 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. (C) 2002 Elsevier Science B.V. All rights reserved.