Relative contribution of transient receptor potential channels (TRPC)‎ and dihydropyridine-sensitive calcium influx to contractile response of a- adrenergic agonists in rat Aortic Strips

Abstract EN

Background Voltage-operated calcium channels (VOCCs), particularly the dihydropyridine-sensitive L-type are probably the best-characterized calcium entry pathway.

Moreover, in smooth muscle cells, there are several types of calcium-permeable channels which are non-voltage-gated, including the so-called receptor-operated calcium channels (ROCCs), activated by agonists acting on a range of G-proteincoupled receptors, and store-operated calcium channels (SOCCs), activated following depletion of the calcium stores within the sarcoplasmic reticulum.

The ROCCs and SOCCs may be closely related, being formed from proteins of the Transient Receptor Potential Channel (TRPC) family.

However, our knowledge of the functional roles of TRPCs in smooth muscle excitation-contraction coupling is much less advanced than our understanding of VOCCs.

Aim of this study was to determine the relative contribution of TRPCs and dihydropyridine-sensitive VOCCs to isometric contractions of isolated rat aortic strips induced by α-adrenergic agonists in vitro. Results from the present study demonstrated that 1) TRPCs and dihydropyridine-sensitive VOCCs contribute significantly to total active tension developed by norepinephrine (NE, α1 and α α2 agonist), phenylephrine PE, α1 agonist) and clonidine (α2 agonist) in rat thoracic aortic strip; 2) starting from agonist concentrations 10-6 Mup to 10-4M, con-tribution of TRPCs to NE and PE α1- mediated response was of higher significance (P<0.001) than L-type VOCCs (p<0.05), while both channel classes seemed to equally contribute to the α2–mediated response (clonidine); 3) the fast slope of maximal contraction (i.e.

the initial rapid rise in smooth muscle tension) to α1 and α2 agonists was ~ 43-51% cadmium chloride ((CdCl2)-inhibitable suggesting that TRP channels mediate ~50% of the fast tension development; and 4)the subsequent slow sustained phase of rise in muscle tension by α1 adrenoceptors was ~ 79%inhibited by nitrendipine while that of α2 adrenoceptors was 57% inhibited suggesting the dominant role for Ca++ entry via VOCCs in the slow phase.