In afferent arterioles, the signaling events that lead to an increase in cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and initiation of vascular contraction are increasingly being delineated. We have recently studied angiotensin II (Ang II) mediated effects on sarcoplasmic reticulum mobilization of Ca²⁺ and the role of superoxide and cyclic adenosine diphosphoribose (cADPR) in these processes. Now we investigate the participation of transient receptor potential canonical channels (TRPC) and a Na⁺/Ca²⁺ exchanger (NCX) in Ca²⁺ entry mechanisms. Afferent arterioles, isolated with the magnetized polystyrene bead method, were loaded with fura-2 to measure [Ca²⁺]_i ratiometrically. We observed that the Cl_Ca2+ channel blocker niflumic acid (NFA) (10 and 50 µ M) affects neither the peak nor plateau [Ca²⁺]_i response to Ang II. Arterioles were pretreated with ryanodine (100 µM) and TMB-8 to block SR mobilization via the ryanodine receptor (RyR) and IP₃ receptor (IP₃R), respectively. The peak [Ca²⁺]_i response to Ang II was reduced by 40%. Addition of 2APB to block TRPC mediated Ca²⁺ entry inhibited the peak and plateau [Ca²⁺]_i Ang II responses 80% and 74%. Flufenamic acid (FFA) (50 µM), which stimulates TRPC6, caused a sustained increase of [Ca²⁺]_i of 146 nM. This response was unaffected by diltiazem or nifedipine. KB-R7943 (at the low concentration of 10 µM) inhibits reverse (but not forward) mode NCX. KB-R7943 decreased the peak [Ca²⁺]_i response to Ang II by 48% and to FFA by 38%. We conclude that TRPC6 and reverse mode NCX may be important Ca²⁺ entry pathways in afferent arterioles.