Calcium channels: L-type and T-type

Calcium channels: L-type and T-type


Calcium channels in the heart muscle are of two types: L-type (ICa-L) and T-type (ICa-T). Both these are voltage gated calcium channels. L-type channels are involved in the myocardial contraction while T-type channels are involved in impulse generation and conduction. The calcium channels are located in the plasma membrane and are protein complexes that are voltage gated to regulate entry of calcium ions into the cell [1].

Phase 2 or plateau phase of myocardial action potential is featured by influx of calcium ions through L-type calcium channels (ICa-L). In addition to myocardial cells, L-type calcium channels are important in vascular smooth muscle contractility [1].

The depolarization phase of pacemaker cells is mainly due to L-type calcium channels (ICa-L). There is some contribution to the diastolic depolarization phase by T type calcium channels (ICa-T).

All the clinically used calcium channel blockers are L-type calcium channel blockers [1]. Mibefradil, a T-type and L-type calcium channel blocker, was withdrawn from market soon after introduction due to important adverse effects including drug interactions. Mibefradil inhibits the P-450 enzyme CYP 3A4 and interferes with the metabolism of several other medicines [2].

Of a total of six types of calcium channels, only L and T are found in the heart and blood vessels [1]. Other channels are N, P, Q and R types, which are prominent in central and peripheral nervous system.

References

  1. Triggle DJ. The physiological and pharmacological significance of cardiovascular T-type, voltage-gated calcium channels. Am J Hypertens. 1998 Apr;11(4 Pt 3):80S-87S.
  2. Mullins ME, Horowitz BZ, Linden DH, Smith GW, Norton RL, Stump J. Life-threatening interaction of mibefradil and beta-blockers with dihydropyridine calcium channel blockers. JAMA. 1998 Jul 8;280(2):157-8.