Reexpression of T-type Ca2+ channel gene and current in post-infarction remodeled rat left ventricle

Cardiovasc Res. 2000 Jun;46(3):442-9. doi: 10.1016/s0008-6363(00)00017-1.

Abstract

Objective: T-type Ca2+ currents (I(Ca-T)) are present in neonatal rat myocytes but is not detected in adult ventricular myocytes. The present study was designed to investigate the expression of the T-type Ca2+ channel gene and current in post-infarction remodeled hypertrophied rat left ventricle (LV).

Methods: We compared the expression of T-type Ca2+ channel gene alpha-1G in neonatal rat LV, in adult sham-operated LV and remodeled hypertrophied LV 3 to 4 weeks post-myocardial infarction (MI) using RNase protection assay (RPA). The cDNA fragment of alpha-1G used in RPA was obtained from poorly conserved region of recently published T-type Ca2+ channel coding sequence of rat by RT-PCR. The fragment was verified by restriction enzyme digestion and sequencing. The presence of I(Ca-T) in LV of sham and post-MI rats was examined using patch-clamp techniques. In the presence of K+-free, Na+-free external solution, I(Ca-T) was separated from I(Ca-L) by different holding potentials (HP). I(Ca-T) was also recorded during depolarization to -40 mV from a HP of -80 mV with NaCl in external solution and I(Na) suppressed by 100 microM tetrodotoxin (TTX).

Results: The T-type Ca2+ channel gene alpha-1G was expressed in neonatal heart, the expression level decreased by 80%, in adult sham heart and was reexpressed in MI (158% increases compared to sham; P<0.01). I(Ca-T) was recorded in 11 of 31 MI cells in presence of K+-free, Na+-free external solution and in 9 of 14 cells when I(Na) was suppressed by TTX. I(Ca-T) was not detected in any of 21 sham cells. I(Ca-T) density was 1.1+/-0.4 pA/pF. I(Ca-T) was more sensitive to Ni2+ and less sensitive to nisoldipine.

Conclusions: T-type Ca2+ channel gene and current are reexpressed in rat post-MI remodeled LV myocytes. Its functional significance in the post-MI remodeling process remains to be defined.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, T-Type / drug effects
  • Calcium Channels, T-Type / genetics*
  • Calcium Channels, T-Type / metabolism
  • Female
  • Gene Expression
  • Myocardial Infarction / complications*
  • Myocardial Infarction / metabolism
  • Nickel / pharmacology
  • Nisoldipine / pharmacology
  • Patch-Clamp Techniques
  • RNA, Messenger / analysis*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Ventricular Remodeling*

Substances

  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • RNA, Messenger
  • Nisoldipine
  • nickel chloride
  • Nickel